Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the...Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.展开更多
Introduction:Myocardial ischemia-reperfusion(IR)injury has received widespread attention due to its damaging effects.Electroacupuncture(EA)pretreatment has preventive effects on myocardial IR injury.SLC26A4 is a Na+in...Introduction:Myocardial ischemia-reperfusion(IR)injury has received widespread attention due to its damaging effects.Electroacupuncture(EA)pretreatment has preventive effects on myocardial IR injury.SLC26A4 is a Na+independent anion reverse transporter and has not been reported in myocardial IR injury.Objectives:Tofind potential genes that may be regulated by EA and explore the role of this gene in myocardial IR injury.Methods:RNA sequencing and bioinformatics analysis were performed to obtain the differentially expressed genes in the myocardial tissue of IR rats with EA pretreatment.Myocardial infarction size was detected by TTC staining.Serum CK,creatinine kinase-myocardial band,Cardiac troponin I,and lactate dehydrogenase levels were determined by ELISA.The effect of SLC26A4 on cardiomyocyte apoptosis was explored by TUNEL staining and western blotting.The effects of SLC26A4 on inflammation were determined by HE staining,ELISA,and real-time PCR.The effect of SLC26A4 on the NF-κB pathway was determined by western blotting.Results:SLC26A4 was up-regulated in IR rats but downregulated in IR rats with EA pretreatment.Compared with IR rats,those with SLC26A4 knockdown exhibited improved cardiac function according to decreased myocardial infarction size,reduced serum LDH/CK/CK-MB/cTnI levels,and elevated left ventricular ejection fraction and fractional shortening.SLC26A4 silencing inhibited myocardial inflammation,cell apoptosis,phosphorylation,and nuclear translocation of NF-κB p65.Conclusion:SLC26A4 exhibited promoting effects on myocardial IR injury,while the SLC26A4 knockdown had an inhibitory effect on the NF-κB pathway.These results further unveil the role of SLC26A4 in IR injury.展开更多
Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic...Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.展开更多
Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)reg...Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.展开更多
[Objectives]To explore the therapeutic effects and potential mechanisms of Glyasperin A(GAA)on myocardial ischemia(MI)based on network pharmacology and molecular docking.[Methods]The molecular structure of GAA was dow...[Objectives]To explore the therapeutic effects and potential mechanisms of Glyasperin A(GAA)on myocardial ischemia(MI)based on network pharmacology and molecular docking.[Methods]The molecular structure of GAA was downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and all targets of GAA were predicted by converting 3D model molecules into SMILES online tool and Swiss target prediction.Genecards database and DisGeNET database were used to find the targets related to MI,and then Venny 2.1.0 was used to generate the corresponding Wayne diagram,and then Cytoscape 3.9.1 software was used to construct the protein-protein interaction(PPI)network.With the help of DAVID database and Microbiology,the selected core targets were enriched and analyzed by gene ontology(GO),biological process(BP),and Kyoto Encyclopedia of Genes and Genomes(KEGG),and then the molecular docking between GAA and core targets was verified by AutoDock and Pymol software.[Results]A total of 1883 MI targets were screened,and in the protein-protein interaction network,AKT1,PTGS2,PPARG,ESR1,GSK3B were the proteins with higher values.Gene ontology and KEEG enrichment analysis showed that the biological processes involved mainly included inflammatory response,negative regulation of gene expression,and response to exogenous stimuli.Signaling pathways mainly include IL-17 signaling pathway,HIF-1 signaling pathway,and so on.The results of molecular docking showed that the binding energy of GAA and core protein was less than-5 Kcal/mol in four groups.These indicated that GAA with good binding had a certain therapeutic effect on myocardial ischemia.[Conclusions]Based on the systematic network pharmacology method,this study predicts the basic pharmacological effects and potential mechanisms of GAA in the treatment of MI,and reveals that GAA may treat MI through multiple targets and signaling pathways.It is expected to provide a basis for further study of its pharmacological mechanisms.展开更多
The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/re...The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.展开更多
This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reper...This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reperfusion was performed by ligation of the left anterior descending coronary artery for 30 min, fol-lowed by reperfusion for 60 min. The effects of zingiberis and acniti praeparatae decoction on ECG ST segment, myocardial infarction percentage, malondialdehyde （MDA） content in the serum, superoxide dismutase （SOD） activity and other indica-tors were observed. [Result] Zingiberis and acniti praeparatae decoction could effec-tively inhibit ECG ST segment elevation caused by myocardial ischemia-reperfusion injuries, reduce the percentage of myocardial infarction, decline the content of MDA in the serum, and increase the activity of SOD. [Conclusion] Zingiberis and acniti praeparatae decoction exhibits protective effects on oxidative injuries caused by my-ocardial ischemia-reperfusion injuries in rats, which may be involved in reducing the formation of myocardial free radicals and enhancing antioxidant capacity of my-ocardium.展开更多
AIM： To observe the effect of electroacupuncture （EA） of ＂Neiguan＂ （PC6） and ＂Gongsun＂ （SP4） on pathological changes of the heart and stomach in rats with acute myocardial ischemia （AMI）, and to explore i...AIM： To observe the effect of electroacupuncture （EA） of ＂Neiguan＂ （PC6） and ＂Gongsun＂ （SP4） on pathological changes of the heart and stomach in rats with acute myocardial ischemia （AMI）, and to explore its underlying mechanism. METHODS： Fifty Wistar rats were randomized into control, model, PC6, SP4 and PC6 ＋ SP4 groups （n = 8 each group）. An AMI model was established by occlusion of the descending anterior branch （DAB） of the left coronary artery. ECG-ST of cervico-thoracic lead and electrogastrogram （EGG） were recorded. EA was applied to PC6, SP4 and PC6 ＋ SP4 groups, respectively. At the end of experiments, the rats were transcardicalty perfused with 4% paraformaldehyde, and the heart base myocardium, gastric antrum and duodenum tissues were sampled, sectioned and stained with a reduced form of nicotinamideadenine dinucleotide phosphate （NADPH）-diaphorase histochemical method for displaying nitric oxide synthase （NOS） activity. RESULTS： After AMI, ECG-ST values elevated. After EA, the elevated ECG-ST values at 20 min in PC6group, at 30 min in PC6 ＋ SP4 and SP4 groups had no significant differences in comparison with their respective basal values before AMI. Following AMI, the amplitude and frequency of slow waves of EGG decreased remarkably （P 〈 0.05）. At 30 min after EA, the mean amplitude and frequency of slow waves of EGG in the three EA groups had no marked differences compared with their individual basal levels and those in the control group. After AMI, the mean integral grey values of NOS-positive product in myocardium, gastric antrum and duodenum tissues in the model group increased remarkably in comparison with the control group, while those in three EA groups were lower than those in the model group. No significant differences were found in ECG-ST and EGG improvement among the three EA groups. However, EA of PC6 had a better effect on ECG-ST and EA of PC4 had a better effect on EGG, respectively. CONCLUSION： EA of PC6, SP4 and PC6 ＋ SP4 can significantly promote the recovery of cardiac and gastric electrical activities after AMI, and up-regulate NOS expression in myocardium, gastric antrum and duodenum tissues.展开更多
BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technol...BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,P<0.05;N:9.27±4.75×10^(9)/L vs.3.89±0.81×10^(9)/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.展开更多
Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury,but this approach is limited by their poor viability after transplantation.The present study was to investi...Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury,but this approach is limited by their poor viability after transplantation.The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia,as well as survival,differentiation,and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI).MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope,and by using flow cytometry following culture in serumfree medium and exposure to hypoxia (5% CO2,95% N2) for 12 h with or without TMZ.Thirty Wistar rats were divided into 3 groups (n=10 each group),including groupⅠ(AMI control),groupⅡ (MSCs transplantation alone),and group Ⅲ (TMZ+MSCs).Rat MSCs (4×107) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation.The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg?kg-1?day-1) from day 3 before AMI to day 28 after AMI.Cardiac structure and function were assessed by echocardiography at 28th day after transplantation.Blood samples were collected before the start of TMZ therapy (baseline),and 24 and 48 h after AMI,and inflammatory cytokines (CRP,TNF-α) were measured.Then the sur-vival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining.The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay.Furthermore,apoptosis-related proteins (Bcl-2,Bax) within the post-infarcted myocardium were detected by using Western blotting.In hypoxic culture,the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serumfree medium and hypoxia environment.In vivo,cardiac infarct size was significantly reduced,and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group.Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis,further increased MSCs viability,further decreased infarct size,and further improved cardiac function as compared with MSCs alone.The baseline levels of inflammatory cyto-kines (CRP,TNF-α) had no significant difference among the groups.In contrast,all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group.Furthermore,Western blotting indicated that the expression of antiapoptotic protein Bcl-2 was upregulated,while the proapoptotic protein Bax was down-regulated in the TMZ+MSCs group,compared with that in the MSCs group.It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.展开更多
There is an urgent need to elucidate the pathogenesis of myocardial ischemia(MI)and potential drug treatments.Here,the anti-MI mechanism and material basis of Ginkgo biloba L.extract(GBE)were studied from the perspect...There is an urgent need to elucidate the pathogenesis of myocardial ischemia(MI)and potential drug treatments.Here,the anti-MI mechanism and material basis of Ginkgo biloba L.extract(GBE)were studied from the perspective of energy metabolism flux regulation.Metabolic flux analysis(MFA)was performed to investigate energy metabolism flux disorder and the regulatory nodes of GBE components in isoproterenol(ISO)-induced ischemia-like cardiomyocytes.It showed that[U-13 C]glucose derived m+2 isotopologues from the upstream tricarboxylic acid(TCA)cycle metabolites were markedly accumulated in ISO-injured cardiomyocytes,but the opposite was seen for the downstream metabolites,while their total cellular concentrations were increased.This indicates a blockage of carbon flow from glycolysis and enhanced anaplerosis from other carbon sources.A Seahorse test was used to screen for GBE components with regulatory effects on mitochondrial aerobic respiratory dysfunction.It showed that bilobalide protected against impaired mitochondrial aerobic respiration.MFA also showed that bilobalide significantly modulated the TCA cycle flux,reduced abnormal metabolite accumulation,and balanced the demand of different carbon sources.Western blotting and PCR analysis showed that bilobalide decreased the enhanced expression of key metabolic enzymes in injured cells.Bilobalide’s efficacy was verified by in vivo experiments in rats.This is the first report to show that bilobalide,the active ingredient of GBE,protects against MI by rescuing impaired TCA cycle flux.This provides a new mechanism and potential drug treatment for MI.It also shows the potential of MFA/Seahorse combination as a powerful strategy for pharmacological research on herbal medicine.展开更多
Erigeron multiradiatus(Lindl.)Benth.,has been used in Tibet folk medicine to treat various inflammatory diseases.The aim of this study was to investigate anti-myocardial ischemia and reperfusion(I/R)injury effect of c...Erigeron multiradiatus(Lindl.)Benth.,has been used in Tibet folk medicine to treat various inflammatory diseases.The aim of this study was to investigate anti-myocardial ischemia and reperfusion(I/R)injury effect of caffeoylquinic acids derivatives of E.multiradiatus(AE)in vivo and to explain underling mechanism.AE was prepared using the whole plant of E.multiradiatus and contents of 6 caffeoylquinic acid determined through HPLC analysis.Myocardial I/R were induced by left anterior descending coronary artery occlusion for 30 min followed by 24 h of reperfusion in rats.AE administration(10,20 and 40 mg·kg-1)inhibited I/R-induced injury as indicated by decreasing myocardial infarct size,reducing of CK and LDH activities and preventing ST-segment depression in dose-dependent manner.AE decreased cardiac tissue levels of pro-inflammatory factors TNF-αand IL-6 and attenuated leukocytes infiltration.AE was further demonstrated to significantly inhibit I-κB degradation,nuclear translocation of p-65 and phosphorylation of JNK.Our results suggested that cardioprotective effect of AE could be due to suppressing myocardial inflammatory response and blocking NF-κB and JNK activation pathway.Thus,caffeoylquinic acids might be the active compounds in E.multiradiatus on myocardial ischemia and be a potential natural drug for treating myocardial I/R injury.展开更多
Objective: To study the effect of fructose 1,6-diphosphate(FDP) on myocardial ischemia reperfusion injury in rats and its molecular mechanism.Methods: Male SPF SD rats were selected as experimental animals and randoml...Objective: To study the effect of fructose 1,6-diphosphate(FDP) on myocardial ischemia reperfusion injury in rats and its molecular mechanism.Methods: Male SPF SD rats were selected as experimental animals and randomly divided into four groups.Sham group received sham operation, I/R group were made into myocardial ischemia reperfusion injury models, FDP group were made into myocardial ischemia reperfusion injury models and then were given FDP intervention, and FDP+AG490 group were made into myocardial ischemia reperfusion injury models and then were given FDP and JAK2 inhibitor AG490 intervention.Results: CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of I/R group were significantly higher than those of Sham group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissues were significantly lower than those of Sham group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP group were significantly lower than those of I/R group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissue were significantly higher than those of I/R group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP+AG490 group were significantly higher than those of FDP group whereas Bcl-2 protein expression in myocardial tissue was significantly lower than that of FDP group.Conclusion: FDP could reduce the myocardial ischemia reperfusion injury in rats by activating the JAK2/STAT3 pathway.展开更多
The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization(TDR)under acute myocardial ischemia in intact canine was investigated.Using the monophasic action potential(MAP)recording t...The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization(TDR)under acute myocardial ischemia in intact canine was investigated.Using the monophasic action potential(MAP)recording technique,MAPs of the epicardium(Epi),midmyocardium(Mid)and endocardium(Endo)were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs.MAPD 90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization(EAD)before autonomic nervous stimulation and during autonomic nervous stimulation were compared.It was found that 10 min after acute myocardial ischemia,TDR was increased from 55±8 ms to 86±15 ms during sympathetic stimulation(P<0.01).The TDR(53±9 ms)during parasympathetic stimulation was not significantly different from that of the control(55±8 ms)(P>0.05).The EAD was elicited in the Mid of 2 dogs(16%)10 min after acute myocardial ischemia,but the EAD were elicited in the Mid of 7 dogs(58%)during sympathetic stimulation(P<0.01).It was concluded that:(1)Sympathetic stimulation can increase the transmural dispersion of repolari-zation and induce early afterdepolarizations in the Mid under acute myocardial ischemia,which provide the opportunity for the ventricular arrhythmia developing;(2)Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.展开更多
Myocardial ischemia/reperfusion injury can lead to severe brain injury.Glycogen synthase kinase 3 beta is known to be involved in myocardial ischemia/reperfusion injury and diabetes mellitus.However,the precise role o...Myocardial ischemia/reperfusion injury can lead to severe brain injury.Glycogen synthase kinase 3 beta is known to be involved in myocardial ischemia/reperfusion injury and diabetes mellitus.However,the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear.In this study,we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats.Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin.Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery.Post-conditioning comprised three cycles of ischemia/reperfusion.Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion,the structure of the brain was seriously damaged in the experimental rats compared with normal controls.Expression of Bax,interleukin-6,interleukin-8,terminal deoxynucleotidyl transferase d UTP nick end labeling,and cleaved caspase-3 in the brain was significantly increased,while expression of Bcl-2,interleukin-10,and phospho-glycogen synthase kinase 3 beta was decreased.Diabetes mellitus can aggravate inflammatory reactions and apoptosis.Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes.Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glycogen synthase kinase 3 beta.According to these results,glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.展开更多
The application of the laser Raman spectroscopic（LRS） technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol（ISO） was described.Animal model of myocardial ischemia ...The application of the laser Raman spectroscopic（LRS） technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol（ISO） was described.Animal model of myocardial ischemia was established for rats induced by ISO.Rats were randomly divided into four groups as normal group and myocardial ischemia groups.We observed the successful myocardial ischemia model via serum enzymes levels and hematoxylin-eosin（HE） staining,and detected the liver tissue of the rats from normal group and liver tissue of the rats from myocardial ischemia groups via UV-Vis spectroscopy（UV-Vis） and LRS,and the changes of the absorbance spectra were compared in the above four different groups.The results show that ISO can induce rat myocardial ischemia successfully.The spectrum of normal liver tissue supernatant exhibits a strong absorption band at 968 nm,but no absorption band appears in the spectra of liver tissue supernatant solutions from the rats with myocardial ischemia induction after 2,12 and 72 h presented at 968 nm.LRS results show that Raman intensities of the precipitates suffered from ISO-treatment after 2,12 and 72 h were obviously increased compared with that of the precipitate of the liver tissue of the normal rats suffered from 0.9 g/L normal saline（NS） treatment.These results indicate that LRS and UV-Vis can be harmless,nondestructive,rapid and effective methods for analyzing different pathological specimens of liver tissue from myocardial ischemia rats.展开更多
Effect of Siqi decoction on myocardial ischemia is to prevent cardiac myocyte membrane from damage associated with oxygen free radicals related to NO. To research the regulatoin of the content of malondialdehyde by Si...Effect of Siqi decoction on myocardial ischemia is to prevent cardiac myocyte membrane from damage associated with oxygen free radicals related to NO. To research the regulatoin of the content of malondialdehyde by Siqi decoction, an index of lipid peroxidation, via increasing activity of superoxide dismutase in blood serum of rats with Myocardial Ischemia, the model of myocardium ischemia was made in Wistar rats with posterior pituitary injection through vein in tail. Siqi decoction, Diaoxinxuekang（DK） and Fufangdanshenpian（FD）, the latter two drugs of which are effective TCM drugs of anti-myocardial ischemia at present, were administrated to the rats with myocardium ischemia for 5 days to compare the effect of them on myocardium ischemia as reference drugs via measuring the changes of the content of malondialdehyde and the activity of superoxide dismutase in the rat blood serum with myocardial ischemia. There were a remarkable increase in the activity of superoxide dismutase and a decrease in the content of malondialdehyde in the serum of the rats administered Siqi decoction compared with those of the rats in control group, p〈0.05. The contents of MDA in the serum of the prevention group rats in the experiments are lower than those of the cure group rats. Anti-Myocardium Ischemia mechanism of Siqi decoction is the regulation of the content of malondialdehyde via increasing activity of superoxide dismutase in the serum of Rats with myocardial ischemia and stimulating the activity of NOS in serum so as to increase NO concentration.展开更多
Objective: Coronary artery was ligated to study the characteristics of myocardial ischemia in rats. Methods: The left anterior descending artery was ligated to establish the rat model of acute myocardial ischemia. All...Objective: Coronary artery was ligated to study the characteristics of myocardial ischemia in rats. Methods: The left anterior descending artery was ligated to establish the rat model of acute myocardial ischemia. All animals were divided into normal control group, sham operation group and model group. 1, 2 and 4 weeks after modeling, ECG (II lead) was recorded, the weight of whole heart and left ventricle were recorded and organ indexes were calculated;myocardial infarct size was determined by TTC;CK, CK-MB, LDH, AST contents of serum were detected;cardiac function was determined by left ventricular intubation via carotid artery and left ventricular was taken to perform pathological observation. Results: 1 week after modeling, compared with the sham operation group, the ECG and heart function index of rats model had significant change, but the myocardial enzymes did not change significantly;4 weeks after modeling, the ECG and cardiac function of animal models had a recovery trend, but the myocardial enzymes, including CK, CK-MB, LDH, AST, were significantly increased;1 week after modeling, the left ventricular indexes of model rats were increased;the infarct size was about 30%, myocardial cell necrosis and granulation tissue hyperplasia could be observed in infarction area;with the modeling time extended, from 2 to 4 weeks, the left ventricular and heart indexes of model group were significantly increased;the infarct size was relatively constant, left ventricular became thickly, and fibrous or granulation tissue was significantly proliferated in infarction area under microscope. Conclusion: The indexes of myocardial ischemia induced by coronary artery ligation in rats are different at different time points. The results suggest that the time point should be selected to observe the anti-myocardial ischemia effect of the subjects from different aspects.展开更多
Objective:To investigate the protective effect of sinomenine stellate ganglion block(SGB)on chronic myocardial ischemia and its related mechanism.Methods:SD male and female rats(180~200g)were randomly divided into fou...Objective:To investigate the protective effect of sinomenine stellate ganglion block(SGB)on chronic myocardial ischemia and its related mechanism.Methods:SD male and female rats(180~200g)were randomly divided into four groups:blank group,model group,lidocaine group,lidocaine+sinomenine group.The rats in blank group were fed with normal standard diet without modeling,and the other rats were fed with high-fat diet.After 8 weeks of feeding,the rats in high-fat diet group were significantly different from those in blank control group.Then they were randomly divided into 3 groups,10 rats in model group were injected with 0.9%NaCl into right stellate ganglion(RSG)After 2 weeks of continuous injection,pituitrin injection was continuously injected into sublingual vein of rats for 3 days,once every 24 hours;lidocaine group rats were injected with 0.24 mL 1%lidocaine injection in RSG,the rest was the same as model group;lidocaine+sinomenine group rats were injected with 0.24 mL 1%lidocaine injection+0.095 mL sinomenine hydrochloride+2.9 mL 0.8 mL 0.8 mL in RSG,the rest was the same as model group.At the end of the eighth week of the experiment,the rats in the high-fat diet feeding group and the standard ordinary diet feeding group were given the medicine after there was significant difference in blood lipid;before the third injection of pituitrin,the ECG changes of the rats in each group were observed;the general situation of the rats before and after the administration was observed;after the experiment,the blood of the rats in each group was taken from the abdominal aorta,and the serum oxidative stress indexes,such as total superoxide dismutase(SOD)and malondialdehyde,were detected(MDA,IL-6 and cTnI were measured.Results:compared with the blank group,the ECG of the model group changed significantly(P<0.01),the cTnI value increased significantly(P<0.01),indicating that the rat myocardial ischemia model was successfully established;compared with the model group,the SOD level of lidocaine group and lidocaine+sinomenine group increased significantly(P<0.05,P<0.01),the MDA level decreased significantly(P<0.05,P<0.01),IL-6 decreased significantly(P<0.05,P<0.01)05,P<0.01).Conclusion:sinomenine SGB has protective effect on rats with chronic myocardial ischemia,which is related to anti oxidative stress and inhibition of inflammatory reaction.展开更多
In the present paper, effects of electroacupuncture (EA) of 3 points of the Heart Meridian and other 3 points of the Lung Meridian on changes of electrocardiogram (ECG), small intestinal electrogram (SIG) and electroe...In the present paper, effects of electroacupuncture (EA) of 3 points of the Heart Meridian and other 3 points of the Lung Meridian on changes of electrocardiogram (ECG), small intestinal electrogram (SIG) and electroencephalogram (EEG) in intravenous drip of pituitrin induced myocardial ischemia rabbits. The three points of the Heart Meridian are "Shenmen" (HT 7), "Lingdao" (HT 4) and one point between HT 7 and HT 4, the 3 points of the Lung Meridian are "Taiyuan"(LU 9), Lieque (LU 7) and one point between LU 9 and LU 7. These points are punctured with filiform needles and stimulated electrically by setting the parameters being frequency of 2.5 Hz, dense sparse waves and duration of 10 min. Results display that the regulative effect of EA of the Heart Meridian is superior to that of EA of the Lung Meridian on the three indexes, showing a closer correlation between the whole Heart Meridian and activities of ECG, SIG and EEG.展开更多
基金supported by the National Natural Science Foundation of China(81870259,82170431,81903608,and U21A20339)the CAMS Innovation Fund for Medical Sciences(CIFMS+1 种基金2019-I2M-5-078)the Postdoctoral Research Foundation of Heilongjiang Province(LBH-Q20148).
文摘Myocardial ischemia is a serious threat to human health,and vascular dysfunction is its main cause.Buxu Tongyu(BXTY)Granule is an effective traditional Chinese medicine(TCM)for treating myocardial ischemia.However,the underlying mechanism of BXTY is still unclear.In this study,we demonstrate that BXTY ameliorates myocardial ischemia by activating the soluble guanylate cyclase(sGC)-30,50-cyclic guanosine monophosphate(cGMP)-protein kinase G(PKG)signaling pathway in vascular smooth muscle cells(VSMCs)to dilate the arteries.BXTY was given by gavage for ten consecutive days before establishing an animal model of acute myocardial ischemia in mice via the intraperitoneal injection of pituitrin.The results showed that BXTY alleviated the symptoms of myocardial ischemia induced by pituitrin in mice,including electrocardiogram abnormalities and changes in plasma enzymes.In addition,BXTY dilated pre-constricted blood vessels and inhibited the vasoconstriction of the superior mesenteric artery in a dose-dependent but endothelial-independent manner.These effects were eliminated by preincubating vascular rings with the sGC inhibitors NS 2028 or ODQ,or with the PKG inhibitor KT 5823.Moreover,BXTY increased the protein expression of sGC-b1 and the intracellular second messenger cGMP level in mouse aortic vascular smooth muscle cells(MOVAs).NS 2028 or ODQ reversed these effects of BXTY.The expression level of the cGMP downstream effector protein PKG-1 increased after treating MOVAs with BXTY.NS 2028,ODQ,or KT 5823 also reversed this effect of BXTY.In conclusion,BXTY can improve the symptoms of acute myocardial ischemia in mice,and activating the sGC-cGMP-PKG pathway in VSMCs to induce vasodilation is its key pharmacodynamic mechanism.
基金This study was funded by the Joint Guidance Project of Heilongjiang Provincial Natural Science Foundation of China(LH2023H063)the Scientific Research Project of Academic Thought Inheritance of Chinese Medicine Great Master of Heilongjiang Provincial Administration of Traditional Chinese Medicine(ZHY2023-151).
文摘Introduction:Myocardial ischemia-reperfusion(IR)injury has received widespread attention due to its damaging effects.Electroacupuncture(EA)pretreatment has preventive effects on myocardial IR injury.SLC26A4 is a Na+independent anion reverse transporter and has not been reported in myocardial IR injury.Objectives:Tofind potential genes that may be regulated by EA and explore the role of this gene in myocardial IR injury.Methods:RNA sequencing and bioinformatics analysis were performed to obtain the differentially expressed genes in the myocardial tissue of IR rats with EA pretreatment.Myocardial infarction size was detected by TTC staining.Serum CK,creatinine kinase-myocardial band,Cardiac troponin I,and lactate dehydrogenase levels were determined by ELISA.The effect of SLC26A4 on cardiomyocyte apoptosis was explored by TUNEL staining and western blotting.The effects of SLC26A4 on inflammation were determined by HE staining,ELISA,and real-time PCR.The effect of SLC26A4 on the NF-κB pathway was determined by western blotting.Results:SLC26A4 was up-regulated in IR rats but downregulated in IR rats with EA pretreatment.Compared with IR rats,those with SLC26A4 knockdown exhibited improved cardiac function according to decreased myocardial infarction size,reduced serum LDH/CK/CK-MB/cTnI levels,and elevated left ventricular ejection fraction and fractional shortening.SLC26A4 silencing inhibited myocardial inflammation,cell apoptosis,phosphorylation,and nuclear translocation of NF-κB p65.Conclusion:SLC26A4 exhibited promoting effects on myocardial IR injury,while the SLC26A4 knockdown had an inhibitory effect on the NF-κB pathway.These results further unveil the role of SLC26A4 in IR injury.
基金funded by Scientific and Technological Planning Project of Guangzhou City(Grant No.201803010115)Projects of The National Natural Science Foundation of China(Grant No.82173972)+1 种基金2021 Traditional Chinese Medicine(Medicine of South China)Industry Talents Project-Innovation Team of South China Medicine Resources,Guangdong Provincial Basic and Applied Basic Research Fund(Grant No.2023A1515011147)supported by the Key Unit of Chinese Medicine Digitalization Quality Evaluation of State Administration of Traditional Chinese Medicine.
文摘Background:Shenzao dripping pill(SZDP)is empirically prescribed for treating cardiac diseases.Nevertheless,there is a lack of comprehensive knowledge regarding the underlying mechanisms contributing to its therapeutic effects.The objective of this study is to investigate the underlying mechanism of SZDP against chronic myocardial ischemia(CMI)in a rat model.Methods:In this study,we utilized electrocardiographic and echocardiographic detection along with pathological tissue analysis to evaluate the efficacy of SZDP.The integration of network pharmacology and metabolomics was conducted to investigate the mechanisms.Molecular docking and molecular dynamics simulations were used to validate the binding energy between the compounds of SZDP and the associated targets.Results:The results showed that SZDP was able to improve T wave voltage,reverse CMI abnormalities in ejection fraction and fractional shortening,and restore histopathological heart damage.Metabolomics results indicated that disturbances of metabolic profile in CMI rats were partly corrected after SZDP administration,mainly affecting purine metabolism.13-Docosenamide may be the potential metabolic biomarker of the therapeutic application of SZDP for CMI.Integrating network pharmacology and metabolomics,thiopurine S-methyltransferase(TPMT),xanthine dehydrogenase/oxidase(XDH),bifunctional purine biosynthesis protein ATIC(ATIC),and cytochrome p4501A1(CYP1A1)were identified as possible targets of SZDP to exert therapeutic effects by enhancing the metabolic levels of L-Tryptophan,Deoxyribose 1-phosphate and Phosphoribosyl formamidocarboxamide.Conclusion:SZDP has a therapeutic effect on CMI by regulating metabolite levels,acting on the targets of TMPT,XDH,ATIC,and CYP1A1,and reducing cardiomyocyte injury and myocardial fibrosis.
基金This work was supported in part by the National Natural Science Foundation of China(82370417,81970320,82270273)the Certificate of China Postdoctoral Science Foundation Grant(2021M693826)+1 种基金the postdoctoral funding from Heilongjiang Province(21042230046)the Hai Yan Youth Fund from Harbin Medical University Cancer Hospital(JJQN2021-09).
文摘Objective:Myocardial ischemia-reperfusion injury(MIRI)is one of the leading causes of death from cardiovascular disease in humans,especially in individuals exposed to cold environments.Long non-coding RNAs(lncRNAs)regulate MIRI through multiple mechanisms.This study explored the regulatory effect of lncRNA-AK138945 on myocardial ischemia-reperfusion injury and its mechanism.Methods:In vivo,8-to 12-weeks-old C57BL/6 male mice underwent ligation of the left anterior descending coronary artery for 50 minutes followed by reperfusion for 48 hours.In vitro,the primary cultured neonatal mouse ventricular cardiomyocytes(NMVCs)were treated with 100μmol/L hydrogen peroxide(H_(2)O_(2)).The knockdown of lncRNA-AK138945 was evaluated to detect cardiomyocyte apoptosis,and a glucose-regulated,endoplasmic reticulum stress-related protein 94(GRP94)inhibitor was used to detect myocardial injury.Results:We found that the expression level of lncRNA-AK138945 was reduced in MIRI mouse heart tissue and H2O2-treated cardiomyocytes.Moreover,the proportion of apoptosis in cardiomyocytes increased after lncRNA-AK138945 was silenced.The expression level of Bcl2 protein was decreased,and the expression level of Bad,Caspase 9 and Caspase 3 protein was increased.Our further study found that miR-1a-3p is a direct target of lncRNA-AK138945,after lncRNA-AK138945 was silenced in cardiomyocytes,the expression level of miR-1a-3p was increased while the expression level of its downstream protein GRP94 was decreased.Interestingly,treatment with a GRP94 inhibitor(PU-WS13)intensified H2O2-induced cardiomyocyte apoptosis.After overexpression of FOXO3,the expression levels of lncRNA-AK138945 and GRP94 were increased,while the expression levels of miR-1a-3p were decreased.Conclusion:LncRNA-AK138945 inhibits GRP94 expression by regulating miR-1a-3p,leading to cardiomyocyte apoptosis.The transcription factor Forkhead Box Protein O3(FOXO3)participates in cardiomyocyte apoptosis induced by endoplasmic reticulum stress through up-regulation of lncRNA-AK138945.
基金Supported by Project of Science and Technology department of Guizhou Province([2019]1401)Guizhou Administration of Traditional Chinese Medicine(QZYY-2021-03)Guizhou Provincial Health Commission(gzwkj2021-464).
文摘[Objectives]To explore the therapeutic effects and potential mechanisms of Glyasperin A(GAA)on myocardial ischemia(MI)based on network pharmacology and molecular docking.[Methods]The molecular structure of GAA was downloaded from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),and all targets of GAA were predicted by converting 3D model molecules into SMILES online tool and Swiss target prediction.Genecards database and DisGeNET database were used to find the targets related to MI,and then Venny 2.1.0 was used to generate the corresponding Wayne diagram,and then Cytoscape 3.9.1 software was used to construct the protein-protein interaction(PPI)network.With the help of DAVID database and Microbiology,the selected core targets were enriched and analyzed by gene ontology(GO),biological process(BP),and Kyoto Encyclopedia of Genes and Genomes(KEGG),and then the molecular docking between GAA and core targets was verified by AutoDock and Pymol software.[Results]A total of 1883 MI targets were screened,and in the protein-protein interaction network,AKT1,PTGS2,PPARG,ESR1,GSK3B were the proteins with higher values.Gene ontology and KEEG enrichment analysis showed that the biological processes involved mainly included inflammatory response,negative regulation of gene expression,and response to exogenous stimuli.Signaling pathways mainly include IL-17 signaling pathway,HIF-1 signaling pathway,and so on.The results of molecular docking showed that the binding energy of GAA and core protein was less than-5 Kcal/mol in four groups.These indicated that GAA with good binding had a certain therapeutic effect on myocardial ischemia.[Conclusions]Based on the systematic network pharmacology method,this study predicts the basic pharmacological effects and potential mechanisms of GAA in the treatment of MI,and reveals that GAA may treat MI through multiple targets and signaling pathways.It is expected to provide a basis for further study of its pharmacological mechanisms.
基金supported by the National Natural Science Foundation of China(Grant Nos.:81970245,82270357,and 81770432)the Scientific Research Project of Shaanxi Administration of Traditional Chinese Medicine,China(Grant Nos.:2021-04-ZZ-001,2021-QYPT-003,and 2022-SLRH-YQ-004)+1 种基金the Project of Science and Technology Department of Shaanxi Province in China(Project No.:2022YWZX-PG-01)the Natural Science Basic Research Program of Shaanxi Province in China(Grant No.:2023-JC-JQ-61).
文摘The canonical transient receptor potential channel(TRPC)proteins form Ca^(2+)-permeable cation channels that are involved in various heart diseases.However,the roles of specific TRPC proteins in myocardial ischemia/reperfusion(I/R)injury remain poorly understood.We observed that TRPC1 and TRPC6 were highly expressed in the area at risk(AAR)in a coronary artery ligation induced I/R model.Trpc1/mice exhibited improved cardiac function,lower serum Troponin T and serum creatine kinase level,smaller infarct volume,less fibrotic scars,and fewer apoptotic cells after myocardial-I/R than wild-type or Trpc6/mice.Cardiomyocyte-specific knockdown of Trpc1 using adeno-associated virus 9 mitigated myocardial I/R injury.Furthermore,Trpc1 deficiency protected adult mouse ventricular myocytes(AMVMs)and HL-1 cells from death during hypoxia/reoxygenation(H/R)injury.RNA-sequencing-based transcriptome analysis revealed differential expression of genes related to reactive oxygen species(ROS)generation in Trpc1/cardiomyocytes.Among these genes,oxoglutarate dehydrogenase-like(Ogdhl)was markedly downregulated.Moreover,Trpc1 deficiency impaired the calcineurin(CaN)/nuclear factorkappa B(NF-kB)signaling pathway in AMVMs.Suppression of this pathway inhibited Ogdhl upregulation and ROS generation in HL-1 cells under H/R conditions.Chromatin immunoprecipitation assays confirmed NF-kB binding to the Ogdhl promoter.The cardioprotective effect of Trpc1 deficiency was canceled out by overexpression of NF-kB and Ogdhl in cardiomyocytes.In conclusion,our findings reveal that TRPC1 is upregulated in the AAR following myocardial I/R,leading to increased Ca^(2+) influx into associated cardiomyocytes.Subsequently,this upregulates Ogdhl expression through the CaN/NF-kB signaling pathway,ultimately exacerbating ROS production and aggravating myocardial I/R injury.
基金Supported by Scientific Research Project of Guiyang College of Traditional Chinese Medicine[(2010)02]~~
文摘This study aimed to investigate the protective effects of zin-giberis and acniti praeparatae decoction on oxidative stress injury induced by my-ocardial ischemia reperfusion in rats. [Method] Myocardial ischemia-reperfusion was performed by ligation of the left anterior descending coronary artery for 30 min, fol-lowed by reperfusion for 60 min. The effects of zingiberis and acniti praeparatae decoction on ECG ST segment, myocardial infarction percentage, malondialdehyde （MDA） content in the serum, superoxide dismutase （SOD） activity and other indica-tors were observed. [Result] Zingiberis and acniti praeparatae decoction could effec-tively inhibit ECG ST segment elevation caused by myocardial ischemia-reperfusion injuries, reduce the percentage of myocardial infarction, decline the content of MDA in the serum, and increase the activity of SOD. [Conclusion] Zingiberis and acniti praeparatae decoction exhibits protective effects on oxidative injuries caused by my-ocardial ischemia-reperfusion injuries in rats, which may be involved in reducing the formation of myocardial free radicals and enhancing antioxidant capacity of my-ocardium.
基金Supported by The Ministry of Science and Technology of China, preliminarily-selected project of meridian research of national scaling plan, No. Pre-19-211
文摘AIM： To observe the effect of electroacupuncture （EA） of ＂Neiguan＂ （PC6） and ＂Gongsun＂ （SP4） on pathological changes of the heart and stomach in rats with acute myocardial ischemia （AMI）, and to explore its underlying mechanism. METHODS： Fifty Wistar rats were randomized into control, model, PC6, SP4 and PC6 ＋ SP4 groups （n = 8 each group）. An AMI model was established by occlusion of the descending anterior branch （DAB） of the left coronary artery. ECG-ST of cervico-thoracic lead and electrogastrogram （EGG） were recorded. EA was applied to PC6, SP4 and PC6 ＋ SP4 groups, respectively. At the end of experiments, the rats were transcardicalty perfused with 4% paraformaldehyde, and the heart base myocardium, gastric antrum and duodenum tissues were sampled, sectioned and stained with a reduced form of nicotinamideadenine dinucleotide phosphate （NADPH）-diaphorase histochemical method for displaying nitric oxide synthase （NOS） activity. RESULTS： After AMI, ECG-ST values elevated. After EA, the elevated ECG-ST values at 20 min in PC6group, at 30 min in PC6 ＋ SP4 and SP4 groups had no significant differences in comparison with their respective basal values before AMI. Following AMI, the amplitude and frequency of slow waves of EGG decreased remarkably （P 〈 0.05）. At 30 min after EA, the mean amplitude and frequency of slow waves of EGG in the three EA groups had no marked differences compared with their individual basal levels and those in the control group. After AMI, the mean integral grey values of NOS-positive product in myocardium, gastric antrum and duodenum tissues in the model group increased remarkably in comparison with the control group, while those in three EA groups were lower than those in the model group. No significant differences were found in ECG-ST and EGG improvement among the three EA groups. However, EA of PC6 had a better effect on ECG-ST and EA of PC4 had a better effect on EGG, respectively. CONCLUSION： EA of PC6, SP4 and PC6 ＋ SP4 can significantly promote the recovery of cardiac and gastric electrical activities after AMI, and up-regulate NOS expression in myocardium, gastric antrum and duodenum tissues.
基金National Natural Science Foundation of China(81670220,31270992,and 30800215)Guangdong Provincial Natural Science Foundation(2014A030313086)+2 种基金Guangdong Provincial Science and Technology Plan Project(2015A020212013)Guangzhou Science and Technology Project(201804010007)This research was approved by the Ethics Committee of the First Affiliated Hospital of Sun Yat-sen University([2019]176).
文摘BACKGROUND:We aimed to investigate the gene expression of myocardial ischemia/reperfusion injury(MIRI)in patients with acute ST-elevation myocardial infarction(STEMI)using stress and toxicity pathway gene chip technology and try to determine the underlying mechanism.METHODS:The mononuclear cells were separated by ficoll centrifugation,and plasma total antioxidant capacity(T-AOC)was determined by the ferric reducing ability of plasma(FRAP)assay.The expression of toxic oxidative stress genes was determined and verified by oligo gene chip and quantitative real-time polymerase chain reaction(qRT-PCR).Additionally,gene ontology(GO)enrichment analysis was performed on DAVID website to analyze the potential mechanism further.RESULTS:The total numbers of white blood cells(WBC)and neutrophils(N)in the peripheral blood of STEMI patients(the AMI group)were significantly higher than those in the control group(WBC:11.67±4.85×10^(9)/L vs.6.41±0.72×10^(9)/L,P<0.05;N:9.27±4.75×10^(9)/L vs.3.89±0.81×10^(9)/L,P<0.05),and WBCs were significantly associated with creatine kinase-myocardial band(CK-MB)on the first day(Y=8.945+0.018X,P<0.05).In addition,the T-AOC was significantly lower in the AMI group comparing to the control group(12.80±1.79 U/mL vs.20.48±2.55 U/mL,P<0.05).According to the gene analysis,eight up-regulated differentially expressed genes(DEGs)included GADD45A,PRDX2,HSPD1,DNAJB1,DNAJB2,RAD50,TNFSF6,and TRADD.Four down-regulated DEGs contained CCNG1,CAT,CYP1A1,and ATM.TNFSF6 and CYP1A1 were detected by polymerase chain reaction(PCR)to verify the expression at different time points,and the results showed that TNFSF6 was up-regulated and CYP1A1 was down-regulated as the total expression.GO and kyoto encyclopedia of genes and genomes(KEGG)enrichment analysis suggested that the oxidative stress genes mediate MIRI via various ways such as unfolded protein response(UPR)and apoptosis.CONCLUSIONS:WBCs,especially neutrophils,were the critical cells that mediating reperfusion injury.MIRI was regulated by various genes,including oxidative metabolic stress,heat shock,DNA damage and repair,and apoptosis-related genes.The underlying pathway may be associated with UPR and apoptosis,which may be the novel therapeutic target.
基金supported by grants from the National Natural Science Foundation of China (No. 30700314)Wuhan Science and Technology Bureau of Hubei province,China (No.20065004116-02)
文摘Bone marrow mesenchymal stem cells (MSCs) have shown potential for cardiac repair following myocardial injury,but this approach is limited by their poor viability after transplantation.The present study was to investigate whether trimetazidine (TMZ) could improve survival of MSCs in an ex vitro model of hypoxia,as well as survival,differentiation,and subsequent activities of transplanted MSCs in rat hearts with acute myocardial infarction (AMI).MSCs at passage 3 were examined for their viability and apoptosis under a transmission electron microscope,and by using flow cytometry following culture in serumfree medium and exposure to hypoxia (5% CO2,95% N2) for 12 h with or without TMZ.Thirty Wistar rats were divided into 3 groups (n=10 each group),including groupⅠ(AMI control),groupⅡ (MSCs transplantation alone),and group Ⅲ (TMZ+MSCs).Rat MSCs (4×107) were injected into peri-infarct myocardium (MSCs group and TMZ+MSCs group) 30 min after coronary artery ligation.The rats in TMZ+MSCs group were additionally fed on TMZ (2.08 mg?kg-1?day-1) from day 3 before AMI to day 28 after AMI.Cardiac structure and function were assessed by echocardiography at 28th day after transplantation.Blood samples were collected before the start of TMZ therapy (baseline),and 24 and 48 h after AMI,and inflammatory cytokines (CRP,TNF-α) were measured.Then the sur-vival and differentiation of transplanted cells in vivo were detected by immunofluorescent staining.The cellular apoptosis in the peri-infarct region was detected by using TUNEL assay.Furthermore,apoptosis-related proteins (Bcl-2,Bax) within the post-infarcted myocardium were detected by using Western blotting.In hypoxic culture,the TMZ-treated MSCs displayed a two-fold decrease in apoptosis under serumfree medium and hypoxia environment.In vivo,cardiac infarct size was significantly reduced,and cardiac function significantly improved in MSCs and TMZ+MSCs groups as compared with those in the AMI control group.Combined treatment of TMZ with MSCs implantation demonstrated further decreased MSCs apoptosis,further increased MSCs viability,further decreased infarct size,and further improved cardiac function as compared with MSCs alone.The baseline levels of inflammatory cyto-kines (CRP,TNF-α) had no significant difference among the groups.In contrast,all parameters at 24 h were lower in TMZ+MSCs group than those in MSCs group.Furthermore,Western blotting indicated that the expression of antiapoptotic protein Bcl-2 was upregulated,while the proapoptotic protein Bax was down-regulated in the TMZ+MSCs group,compared with that in the MSCs group.It is suggested that implantation of MSCs combined with TMZ treatment is superior to MSCs monotherapy for MSCs viability and cardiac function recovery.
基金supported by grants from the National Natural Science Foundation of China(Grant No.:81803496)the CAMS Innovation Fund for Medical Sciences(Grant No.:2016-I2M-3-016)the Applications and Core Technology University Research(ACT-UR,Grant No.:4084)。
文摘There is an urgent need to elucidate the pathogenesis of myocardial ischemia(MI)and potential drug treatments.Here,the anti-MI mechanism and material basis of Ginkgo biloba L.extract(GBE)were studied from the perspective of energy metabolism flux regulation.Metabolic flux analysis(MFA)was performed to investigate energy metabolism flux disorder and the regulatory nodes of GBE components in isoproterenol(ISO)-induced ischemia-like cardiomyocytes.It showed that[U-13 C]glucose derived m+2 isotopologues from the upstream tricarboxylic acid(TCA)cycle metabolites were markedly accumulated in ISO-injured cardiomyocytes,but the opposite was seen for the downstream metabolites,while their total cellular concentrations were increased.This indicates a blockage of carbon flow from glycolysis and enhanced anaplerosis from other carbon sources.A Seahorse test was used to screen for GBE components with regulatory effects on mitochondrial aerobic respiratory dysfunction.It showed that bilobalide protected against impaired mitochondrial aerobic respiration.MFA also showed that bilobalide significantly modulated the TCA cycle flux,reduced abnormal metabolite accumulation,and balanced the demand of different carbon sources.Western blotting and PCR analysis showed that bilobalide decreased the enhanced expression of key metabolic enzymes in injured cells.Bilobalide’s efficacy was verified by in vivo experiments in rats.This is the first report to show that bilobalide,the active ingredient of GBE,protects against MI by rescuing impaired TCA cycle flux.This provides a new mechanism and potential drug treatment for MI.It also shows the potential of MFA/Seahorse combination as a powerful strategy for pharmacological research on herbal medicine.
基金The project supported by the Macao Science and Technology Development Fund(052/2013/A2)
文摘Erigeron multiradiatus(Lindl.)Benth.,has been used in Tibet folk medicine to treat various inflammatory diseases.The aim of this study was to investigate anti-myocardial ischemia and reperfusion(I/R)injury effect of caffeoylquinic acids derivatives of E.multiradiatus(AE)in vivo and to explain underling mechanism.AE was prepared using the whole plant of E.multiradiatus and contents of 6 caffeoylquinic acid determined through HPLC analysis.Myocardial I/R were induced by left anterior descending coronary artery occlusion for 30 min followed by 24 h of reperfusion in rats.AE administration(10,20 and 40 mg·kg-1)inhibited I/R-induced injury as indicated by decreasing myocardial infarct size,reducing of CK and LDH activities and preventing ST-segment depression in dose-dependent manner.AE decreased cardiac tissue levels of pro-inflammatory factors TNF-αand IL-6 and attenuated leukocytes infiltration.AE was further demonstrated to significantly inhibit I-κB degradation,nuclear translocation of p-65 and phosphorylation of JNK.Our results suggested that cardioprotective effect of AE could be due to suppressing myocardial inflammatory response and blocking NF-κB and JNK activation pathway.Thus,caffeoylquinic acids might be the active compounds in E.multiradiatus on myocardial ischemia and be a potential natural drug for treating myocardial I/R injury.
基金supported by Fenghua Science and Technology Bureau(No.B02162715)
文摘Objective: To study the effect of fructose 1,6-diphosphate(FDP) on myocardial ischemia reperfusion injury in rats and its molecular mechanism.Methods: Male SPF SD rats were selected as experimental animals and randomly divided into four groups.Sham group received sham operation, I/R group were made into myocardial ischemia reperfusion injury models, FDP group were made into myocardial ischemia reperfusion injury models and then were given FDP intervention, and FDP+AG490 group were made into myocardial ischemia reperfusion injury models and then were given FDP and JAK2 inhibitor AG490 intervention.Results: CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of I/R group were significantly higher than those of Sham group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissues were significantly lower than those of Sham group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP group were significantly lower than those of I/R group whereas Bcl-2, p-JAK2 and p-STAT3 protein expression in myocardial tissue were significantly higher than those of I/R group; CK, CK-MB, c Tn I and LDH contents in serum as well as Bax and Caspase-3 protein expression in myocardial tissue of FDP+AG490 group were significantly higher than those of FDP group whereas Bcl-2 protein expression in myocardial tissue was significantly lower than that of FDP group.Conclusion: FDP could reduce the myocardial ischemia reperfusion injury in rats by activating the JAK2/STAT3 pathway.
文摘The effect of the autonomic nerves on the transmural dispersion of ventricular repolarization(TDR)under acute myocardial ischemia in intact canine was investigated.Using the monophasic action potential(MAP)recording technique,MAPs of the epicardium(Epi),midmyocardium(Mid)and endocardium(Endo)were recorded simultaneously by specially designed plunge-needle electrodes at the left ventricular free wall under acute myocardial ischemia in 12 open-chest dogs.MAPD 90 and TDR among three myocardial layers as well as the incidence of the early afterdepolarization(EAD)before autonomic nervous stimulation and during autonomic nervous stimulation were compared.It was found that 10 min after acute myocardial ischemia,TDR was increased from 55±8 ms to 86±15 ms during sympathetic stimulation(P<0.01).The TDR(53±9 ms)during parasympathetic stimulation was not significantly different from that of the control(55±8 ms)(P>0.05).The EAD was elicited in the Mid of 2 dogs(16%)10 min after acute myocardial ischemia,but the EAD were elicited in the Mid of 7 dogs(58%)during sympathetic stimulation(P<0.01).It was concluded that:(1)Sympathetic stimulation can increase the transmural dispersion of repolari-zation and induce early afterdepolarizations in the Mid under acute myocardial ischemia,which provide the opportunity for the ventricular arrhythmia developing;(2)Parasympathetic stimulation has no significant effect on the transmural dispersion of repolarization under myocardial ischemia.
基金supported by the National Natural Science Foundation of China,No.81471844the Natural Science Foundation of Hubei Province of China,No.2016CFB167the Basic Scientific Research Foundation of Central Universities,No.2042017kf0147
文摘Myocardial ischemia/reperfusion injury can lead to severe brain injury.Glycogen synthase kinase 3 beta is known to be involved in myocardial ischemia/reperfusion injury and diabetes mellitus.However,the precise role of glycogen synthase kinase 3 beta in myocardial ischemia/reperfusion injury-induced brain injury is unclear.In this study,we observed the effects of glycogen synthase kinase 3 beta on brain injury induced by myocardial ischemia/reperfusion injury in diabetic rats.Rat models of diabetes mellitus were generated via intraperitoneal injection of streptozotocin.Models of myocardial ischemia/reperfusion injury were generated by occluding the anterior descending branch of the left coronary artery.Post-conditioning comprised three cycles of ischemia/reperfusion.Immunohistochemical staining and western blot assays demonstrated that after 48 hours of reperfusion,the structure of the brain was seriously damaged in the experimental rats compared with normal controls.Expression of Bax,interleukin-6,interleukin-8,terminal deoxynucleotidyl transferase d UTP nick end labeling,and cleaved caspase-3 in the brain was significantly increased,while expression of Bcl-2,interleukin-10,and phospho-glycogen synthase kinase 3 beta was decreased.Diabetes mellitus can aggravate inflammatory reactions and apoptosis.Ischemic post-conditioning with glycogen synthase kinase 3 beta inhibitor lithium chloride can effectively reverse these changes.Our results showed that myocardial ischemic post-conditioning attenuated myocardial ischemia/reperfusion injury-induced brain injury by activating glycogen synthase kinase 3 beta.According to these results,glycogen synthase kinase 3 beta appears to be an important factor in brain injury induced by myocardial ischemia/reperfusion injury.
基金Supported by the Scientific and Technological Developing Scheme of Jilin Province,China(No.201101067)
文摘The application of the laser Raman spectroscopic（LRS） technique for the analysis of liver tissues from rats with myocardial ischemia induced by isoproterenol（ISO） was described.Animal model of myocardial ischemia was established for rats induced by ISO.Rats were randomly divided into four groups as normal group and myocardial ischemia groups.We observed the successful myocardial ischemia model via serum enzymes levels and hematoxylin-eosin（HE） staining,and detected the liver tissue of the rats from normal group and liver tissue of the rats from myocardial ischemia groups via UV-Vis spectroscopy（UV-Vis） and LRS,and the changes of the absorbance spectra were compared in the above four different groups.The results show that ISO can induce rat myocardial ischemia successfully.The spectrum of normal liver tissue supernatant exhibits a strong absorption band at 968 nm,but no absorption band appears in the spectra of liver tissue supernatant solutions from the rats with myocardial ischemia induction after 2,12 and 72 h presented at 968 nm.LRS results show that Raman intensities of the precipitates suffered from ISO-treatment after 2,12 and 72 h were obviously increased compared with that of the precipitate of the liver tissue of the normal rats suffered from 0.9 g/L normal saline（NS） treatment.These results indicate that LRS and UV-Vis can be harmless,nondestructive,rapid and effective methods for analyzing different pathological specimens of liver tissue from myocardial ischemia rats.
基金Supported by the National Natural Science Foundation of China(Nos.30570404 and 30670458)the Natural Science Foundation of Jilin Province,China(No.20050561)
文摘Effect of Siqi decoction on myocardial ischemia is to prevent cardiac myocyte membrane from damage associated with oxygen free radicals related to NO. To research the regulatoin of the content of malondialdehyde by Siqi decoction, an index of lipid peroxidation, via increasing activity of superoxide dismutase in blood serum of rats with Myocardial Ischemia, the model of myocardium ischemia was made in Wistar rats with posterior pituitary injection through vein in tail. Siqi decoction, Diaoxinxuekang（DK） and Fufangdanshenpian（FD）, the latter two drugs of which are effective TCM drugs of anti-myocardial ischemia at present, were administrated to the rats with myocardium ischemia for 5 days to compare the effect of them on myocardium ischemia as reference drugs via measuring the changes of the content of malondialdehyde and the activity of superoxide dismutase in the rat blood serum with myocardial ischemia. There were a remarkable increase in the activity of superoxide dismutase and a decrease in the content of malondialdehyde in the serum of the rats administered Siqi decoction compared with those of the rats in control group, p〈0.05. The contents of MDA in the serum of the prevention group rats in the experiments are lower than those of the cure group rats. Anti-Myocardium Ischemia mechanism of Siqi decoction is the regulation of the content of malondialdehyde via increasing activity of superoxide dismutase in the serum of Rats with myocardial ischemia and stimulating the activity of NOS in serum so as to increase NO concentration.
文摘Objective: Coronary artery was ligated to study the characteristics of myocardial ischemia in rats. Methods: The left anterior descending artery was ligated to establish the rat model of acute myocardial ischemia. All animals were divided into normal control group, sham operation group and model group. 1, 2 and 4 weeks after modeling, ECG (II lead) was recorded, the weight of whole heart and left ventricle were recorded and organ indexes were calculated;myocardial infarct size was determined by TTC;CK, CK-MB, LDH, AST contents of serum were detected;cardiac function was determined by left ventricular intubation via carotid artery and left ventricular was taken to perform pathological observation. Results: 1 week after modeling, compared with the sham operation group, the ECG and heart function index of rats model had significant change, but the myocardial enzymes did not change significantly;4 weeks after modeling, the ECG and cardiac function of animal models had a recovery trend, but the myocardial enzymes, including CK, CK-MB, LDH, AST, were significantly increased;1 week after modeling, the left ventricular indexes of model rats were increased;the infarct size was about 30%, myocardial cell necrosis and granulation tissue hyperplasia could be observed in infarction area;with the modeling time extended, from 2 to 4 weeks, the left ventricular and heart indexes of model group were significantly increased;the infarct size was relatively constant, left ventricular became thickly, and fibrous or granulation tissue was significantly proliferated in infarction area under microscope. Conclusion: The indexes of myocardial ischemia induced by coronary artery ligation in rats are different at different time points. The results suggest that the time point should be selected to observe the anti-myocardial ischemia effect of the subjects from different aspects.
基金National Administration of traditional Chinese medicine base project(No.jdzx2012144,jdzx2015253)Shaanxi provincial major disease TCM innovation plan:chest obstruction(coronary heart disease)+1 种基金Shaanxi Provincial Administration of traditional Chinese medicine scientific research project(No.15-scjh015,15-lc016,lcpt089,15-scjh016)discipline innovation team of the Second Affiliated Hospital of Shaanxi University of Chinese medicine(No.2020xktd-b03)。
文摘Objective:To investigate the protective effect of sinomenine stellate ganglion block(SGB)on chronic myocardial ischemia and its related mechanism.Methods:SD male and female rats(180~200g)were randomly divided into four groups:blank group,model group,lidocaine group,lidocaine+sinomenine group.The rats in blank group were fed with normal standard diet without modeling,and the other rats were fed with high-fat diet.After 8 weeks of feeding,the rats in high-fat diet group were significantly different from those in blank control group.Then they were randomly divided into 3 groups,10 rats in model group were injected with 0.9%NaCl into right stellate ganglion(RSG)After 2 weeks of continuous injection,pituitrin injection was continuously injected into sublingual vein of rats for 3 days,once every 24 hours;lidocaine group rats were injected with 0.24 mL 1%lidocaine injection in RSG,the rest was the same as model group;lidocaine+sinomenine group rats were injected with 0.24 mL 1%lidocaine injection+0.095 mL sinomenine hydrochloride+2.9 mL 0.8 mL 0.8 mL in RSG,the rest was the same as model group.At the end of the eighth week of the experiment,the rats in the high-fat diet feeding group and the standard ordinary diet feeding group were given the medicine after there was significant difference in blood lipid;before the third injection of pituitrin,the ECG changes of the rats in each group were observed;the general situation of the rats before and after the administration was observed;after the experiment,the blood of the rats in each group was taken from the abdominal aorta,and the serum oxidative stress indexes,such as total superoxide dismutase(SOD)and malondialdehyde,were detected(MDA,IL-6 and cTnI were measured.Results:compared with the blank group,the ECG of the model group changed significantly(P<0.01),the cTnI value increased significantly(P<0.01),indicating that the rat myocardial ischemia model was successfully established;compared with the model group,the SOD level of lidocaine group and lidocaine+sinomenine group increased significantly(P<0.05,P<0.01),the MDA level decreased significantly(P<0.05,P<0.01),IL-6 decreased significantly(P<0.05,P<0.01)05,P<0.01).Conclusion:sinomenine SGB has protective effect on rats with chronic myocardial ischemia,which is related to anti oxidative stress and inhibition of inflammatory reaction.
文摘In the present paper, effects of electroacupuncture (EA) of 3 points of the Heart Meridian and other 3 points of the Lung Meridian on changes of electrocardiogram (ECG), small intestinal electrogram (SIG) and electroencephalogram (EEG) in intravenous drip of pituitrin induced myocardial ischemia rabbits. The three points of the Heart Meridian are "Shenmen" (HT 7), "Lingdao" (HT 4) and one point between HT 7 and HT 4, the 3 points of the Lung Meridian are "Taiyuan"(LU 9), Lieque (LU 7) and one point between LU 9 and LU 7. These points are punctured with filiform needles and stimulated electrically by setting the parameters being frequency of 2.5 Hz, dense sparse waves and duration of 10 min. Results display that the regulative effect of EA of the Heart Meridian is superior to that of EA of the Lung Meridian on the three indexes, showing a closer correlation between the whole Heart Meridian and activities of ECG, SIG and EEG.
