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
The morbidity and mortality of cardiovascular diseases are very high,which has attracted more and more attention all over the world.Common treatment methods for clinical treatment of acute myocardial infarction includ...The morbidity and mortality of cardiovascular diseases are very high,which has attracted more and more attention all over the world.Common treatment methods for clinical treatment of acute myocardial infarction include direct percutaneous coronary intervention and coronary artery bypass grafting,which can quickly restore blocked coronary blood flow and reduce the infarct size.However,the inevitable ischemia/reperfusion injury will occur during the recovery of coronary blood flow,its pathological mechanism is complicated,and the Western medicine countermeasures are very limited.Among the current drugs for the treatment of cardiovascular diseases,traditional Chinese medicine has become a research hotspot due to its multiple targets,safety,and low side effects.Ginger is the fresh rhizome of Zingiber officinale Rosc.,a perennial herbaceous plant in the ginger family.It is a dual-purpose resource of medicine and food.Ginger has the functions of relieving the appearance and dispelling cold,warming up and relieving vomiting,resolving phlegm and relieving cough,and relieving fish and crab poison.The chemical components of ginger mainly include volatile oil,gingerol,diphenylheptane,etc..Among them,6-gingerol,as the main active component of gingerols,has obvious pharmacological effects in myocardial protection,anti-oxidation,anti-inflammatory,etc..Studies have shown that 6-gingerol protects myocardium mainly through anti-oxidative stress,anti-inflammatory,inhibiting cell apoptosis,and preventing calcium influx.①Anti-oxidative stress:oxidative stress is a state where oxidation and anti-oxidation in the body are out of balance,and it is also an important factor leading to myocardial damage.Many studies have confirmed that 6-gingerol has an antioxidant effect,and it is considered a natural antioxidant.6-gingerol can significantly reduce the degree of oxidative stress and the level of reactive oxygen species caused by cardiomyocyte damage,and has a significant cardioprotective effect.②Anti-inflammatory:inflammation can cause substantial cell damage and organ dysfunction,which is another important cause of myocardial damage.6-gingerol can reduce the levels of inflammatory factors such as interleukin-6,interleukin-1β,and tumor necrosis factor-αin cardiomyocytes,and at the same time inhibit the TLR4/NF-κB signaling pathway,an important regulatory pathway of inflammation,showing that it may improve myocardial damage through anti-inflammatory effects.③Inhibition of apoptosis:apoptosis is a complex and orderly process in the autonomous biochemical process of cells,and one of the main mechanisms of myocardial injury.This process can be roughly divided into three pathways:mitochondria,endoplasmic reticulum,and death receptors.Among them,the mitochondrial pathway plays an important role,and Bcl-2 and Bax located upstream of this pathway can regulate the entire process of cell apoptosis by regulating the permeability of the mitochondrial membrane.Studies have found that the preventive application of 6-gingerol can reduce cell damage,reduce the number of apoptotic cells,reduce the activity of Bax and caspase-3,and increase the expression of Bcl-2.Therefore,6-gingerol pretreatment can reduce the damage of cardiomyocytes,and its mechanism may be related to the inhibition of apoptosis.④Prevent calcium influx:calcium overload is involved in the pathogenesis of myocardial ischemic injury,which may be related to excessive contracture,arrhythmia,and mitochondrial Ca2+accumulation that impairs myocardial function.6-gingerol inhibits the increase of intracellular Ca2+concentration by inhibiting L-type calcium current,thereby reducing extracellular Ca2+influx,thereby avoiding calcium overload and playing a cardioprotective effect.In summary,6-gingerol can effectively treat and improve myocardial ischemia/reperfusion injury,and it has great development potential in the fields of medicine and health products.展开更多
Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were...Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were randomly assigned to the normal control group(NC),model group,ischemia-reperfusion group(IR),hesperidin group,SIRT1 inhibitor group and hesperidin plus SIRT1 inhibitor group.In addition to NC,the rats in the remaining groups were replicated by intraperitoneal of high-fat diet combined with injection of streptozotocin for type 2 diabetic rats.After then,the myocardial ischemia/reperfusion injury(MIRI)rat model was established by LAd for 30 minutes with 2 hours reperfusion.He staining was used to observe the pathological changes of myocardial tissue,and the levels of serum LDH,CK-MB and SOD,GSH and MDA in myocardial tissue were detected by kit methods,and the expression abundance of related proteins in 4-HNE and SIRT1/Nrf2/HO-1 signal pathway were detected by immunohistochemistry and Western blot;Results:Hesperidin could significantly inhibit cardiomyocyte necrosis and inflammatory cell infiltration,reduce LDH activity,CK-MB and MDA level,and increase SOD activity,GSH and 4-HNE level,the differences were statistically significant when compared with IR group(P<0.01).In addition,compared with the ischemia-reperfusion group,the expressions of SIRT1,Nrf2 and HO-1 proteins in hesperidin group were significantly up-regulated,the differences were statistically significant(P<0.01);Conclusion:Hesperidin inhibits oxidative stress by activating SIRT1/Nrf2/HO-1 signaling pathway,and play a protective effect of myocardial ischemia reperfusion injury in diabetic rats.展开更多
Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury(MIRI).Moderate mitophagy can remove damaged mitochondria,inhibit excessive reactive oxygen species a...Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury(MIRI).Moderate mitophagy can remove damaged mitochondria,inhibit excessive reactive oxygen species accumulation,and protect mitochondria from damage.However,excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival,and aggravates cell death.How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane,which mainly include phosphatase and tensin homolog deleted on chromosome ten(PTEN)-induced kinase 1/Parkin,hypoxia-inducible factor-1α/Bcl-2 and adenovirus e1b19k Da interacting protein 3,FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on.In this review,the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI,and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine,thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.展开更多
Autophagy is an evolutionarily conserved process involved in the degradation of long-lived proteins and excessive or dysfunctional organelles. As a pivotal cellular response, autophagy has been extensively studied and...Autophagy is an evolutionarily conserved process involved in the degradation of long-lived proteins and excessive or dysfunctional organelles. As a pivotal cellular response, autophagy has been extensively studied and is known to be involved in various diseases. Ferroptosis is a recently discovered form of regulated cell death characterized by iron overload, leading to the accumulation of lethal levels of lipid hydroperoxides. Recently, an increasing number of studies have revealed a link between autophagy and ferroptosis. Myocardial ischemia/reperfusion injury (MIRI) is an urgent dilemma after myocardial infarction recanalization, which is regulated by several cell death pathways, including autophagy and ferroptosis. However, the potential relationship between autophagy and ferroptosis in MIRI remains unexplored. In this study, we briefly review the mechanisms of autophagy and ferroptosis, including their roles in MIRI. Moreover, we provide an overview of the potential crosstalk in MIRI. Clarifying the relationship between different cell death pathways may provide new ideas for the treatment of MIRI in the future.展开更多
MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of m...MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of miR-208a,while it is challenging to achieve efficient and myocardium-targeted delivery.Herein,biomimetic nanocomplexes(NCs)reversibly coated with red blood cell membrane(RM)were developed for the myocardial delivery of mI.To construct the NCs,membrane-penetrating helical polypeptide(PG)was first adopted to condense mI and form the cationic inner core,which subsequently adsorbed catalase(CAT)via electrostatic interaction followed by surface coating with RM.The membrane-coated NCs enabled prolonged blood circulation after systemic administration,and could accumulate in the injured myocardium via passive targeting.In the oxidative microenvironment of injured myocardium,CAT decomposed H_(2)O_(2)to produce O_(2)bubbles,which drove the shedding of the outer RM to expose the positively charged inner core,thus facilitated effective internalization by cardiac cells.Based on the combined contribution of mI-mediated miR-208a silencing and CAT-mediated alleviation of oxidative stress,NCs effectively ameliorated the myocardial microenvironment,hence reducing the infarct size as well as fibrosis and promoting recovery of cardiac functions.This study provides an effective strategy for the cytosolic delivery of nucleic acid cargoes in the myocardium,and it renders an enlightened approach to resolve the blood circulation/cell internalization dilemma of cell membrane-coated delivery systems.展开更多
Objective:To examine the effect of Shenmai Injection(SMJ)on ferroptosis during myocardial ischemia reperfusion(I/R)injury in rats and the underlying mechanism.Methods:A total of 120SPF-grade adult male SD rats,weighin...Objective:To examine the effect of Shenmai Injection(SMJ)on ferroptosis during myocardial ischemia reperfusion(I/R)injury in rats and the underlying mechanism.Methods:A total of 120SPF-grade adult male SD rats,weighing 220–250 g were randomly divided into different groups according to a random number table.Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion.SMJ was injected intraperitoneally at the onset of 120 min of reperfusion,and erastin(an agonist of ferroptosis),ferrostatin-1(Fer-1,an inhibitor of ferroptosis)and ML385(an inhibitor of nuclear factor erythroid-2 related factor 2(Nrf2))were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments.Cardiac function before ischemia,after ischemia and after reperfusion was analysed.Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed,and the myocardial infarction area was measured.Additionally,the concentration of Fein heart tissues and the levels of creatine kinase-MB(CK-MB),troponin I(cTnI),malondialdehyde(MDA)and superoxide dismutase(SOD)in serum were measured using assay kits,and the expressions of Nrf2,glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)were examined by Western blot.Results:Compared with the sham group,I/R significantly injured heart tissues,as evidenced by the disordered,ruptured and oedematous myocardial fibres;the increases in infarct size,serum CK-MB,cTnI and MDA levels,and myocardial Feconcentrations;and the decreases in SOD activity(P<0.05).These results were accompanied by ultrastructural alterations to the mitochondria,increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling(P<0.05).Compared with the I/R group,pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury,Feconcentrations and ACSL4 expression and attenuated mitochondrial impairment,while 14 mg/kg erastin exacerbated myocardial I/R injury(P<0.05).In addition,cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385,as evidenced by the increased myocardial infarct size,CK-MB,cTnI,MDA and Feconcentrations,and the decreased SOD activity(P<0.05).Conclusions:Ferroptosis is involved in myocardial I/R injury.Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis,thereby providing a strategy for the prevention and treatment of ischemic heart diseases.展开更多
Myocardial ischemia reperfusion(IR)injury is closely related to the overwhelming inflammation in the myocardium.Herein,cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species(ROS)-ultras...Myocardial ischemia reperfusion(IR)injury is closely related to the overwhelming inflammation in the myocardium.Herein,cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species(ROS)-ultrasensitive co-delivery of dexamethasone(Dex)and RAGE small interfering RNA(siRAGE)to attenuate myocardial inflammation.PPTP,a ROSdegradable polycation based on PGE2-modified,PEGylated,ditellurium-crosslinked polyethylenimine(PEI)was developed to surface-decorate the Dex-encapsulated mesoporous silica nanoparticles(MSNs),which simultaneously condensed siRAGE and gated the MSNs to prevent the Dex pre-leakage.Upon intravenous injection to IR-injured rats,the nanotherapeutics could be efficiently transported into the inflamed cardiomyocytes via PGE2-assisted recognition of over-expressed E-series of prostaglandin(EP)receptors on the cell membranes.Intracellularly,the over-produced ROS degraded PPTP into small segments,promoting the release of siRAGE and Dex to mediate effective RAGE silencing(72%)and cooperative antiinflammatory effect.As a consequence,the nanotherapeutics notably suppressed the myocardial fibrosis and apoptosis,ultimately recovering the systolic function.Therefore,the current nanotherapeutics represent an effective example for the codelivery and on-demand release of nucleic acid and chemodrug payloads,and might find promising utilities toward the synergistic management of myocardial inflammation.展开更多
Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills(速效救心丸,SXJ)on myocardial ischemia and reperfusion(I/R)injury.Methods:Mouse myocardial I/R injury model was created by 30-min coro...Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills(速效救心丸,SXJ)on myocardial ischemia and reperfusion(I/R)injury.Methods:Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion,the mice were then divided into the sham group(n=7),the I/R group(n=13),the tirofiban group(TIR,positive drug treatment,n=9),and the SXJ group(n=11).Infarct size(IS),risk region(RR),and left ventricle(LV)were analyzed with double staining methods.In addition,H9C2 rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro.The phosphorylation of extracellular regulated protein kinases1/2(ERK1/2),protein kinase B(AKT),glycogen synthase kinase-3β(GSK3β),and protein expression of GATA4 in nucleus were detected with Western blot assay.Results:The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group(SXJ,22.4%±6.6%;TIR,20.8%±3.3%;vs.I/R,35.4%±3.7%,P<0.05,respectively).In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3βand nuclear expression of GATA4.Conclusion:SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3βand GATA4 signaling pathways.展开更多
Background Myocardial ischemia/reperfusion injury(MI/RI)during myocardial infarction worsens outcomes. It has been proved that ginsenoside Rb1 has a great impact on ischemia/reperfusion(I/R)injury. The aim of this stu...Background Myocardial ischemia/reperfusion injury(MI/RI)during myocardial infarction worsens outcomes. It has been proved that ginsenoside Rb1 has a great impact on ischemia/reperfusion(I/R)injury. The aim of this study is to explore the protective effect of the pretreatment with ginsenoside Rb1 on MI/RI and investigate the underlying mechanisms about the preventive action. Methods A total of 27 healthy adult Sprague-Dawley(SD)rats were randomly divided into 3 groups(n=9 per group):A sham-operated group(Sham n=9);an ischemia 40 min/reperfusion 2 h(I/R n=9)of the cardiac muscle group;Rb1-treated group was divided into 3 subgroups(Rb1 10 mg/kg,20 mg/kg,40 mg/kg,n=3). Ginsenosides Rb1 at different concentrations were injected intraperitoneally for 3 days continuously before ligation. A model of MI/RI was constructed by ligation of the left coronary artery anterior descending branch in rats. Myocardial infarction area after I/R was measured bytriphenyltetrazolium chloride(TTC)staining of myocardial tissue. Hematoxylin and eosin(HE)staining and electrocardiogram indication were used to observe myocardial cell injury and ischemia,respectively. The expression of caspase-8 protein was observed by immunohistochemistry staining. Results The pretreatment of 40 mg/kg dose of ginsenoside Rb1 could decrease the expression of caspase-8 protein caused by I/R and the apoptosis of myocardial cells,improve myocardial ischemia,reduce the area of myocardial infarction and ameliorate MI/RI.Conclusions These results demonstrate that ginsenoside Rb1 has a significant protective effect on MI/RI through attenuating the apoptosis of myocardial cells and improving myocardial ischemia at appropriate dose,which provides new insights into the potential therapy of MI/RI.展开更多
Background The most effective treatment for Acute myocardial infarction(AMI)is timely and effective reperfusion therapy;however,the process of reperfusion therapy can worsen the myocardial damage.This pathological pro...Background The most effective treatment for Acute myocardial infarction(AMI)is timely and effective reperfusion therapy;however,the process of reperfusion therapy can worsen the myocardial damage.This pathological process is known as myocardial ischemia-reperfusion injury(I/R).But,the mechanism of I/R is not fully understood and there is no available effective treatment for I/R.This article will review the mechanisms of occurrence and treatments currently found for I/R.展开更多
Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction,but morbidity and mortality of acute myocardial infarction are still high.Reperfusion injuries are inevitable due ...Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction,but morbidity and mortality of acute myocardial infarction are still high.Reperfusion injuries are inevitable due to the generation of reactive oxygen species(ROS)and apoptosis of cardiac muscle cells.However,many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration,such as short half-life,low stability,low bioavailability,and side effects for treatment myocardial ischemia reperfusion injury.Therefore,it is necessary to develop effective drugs and technologies to address this issue.Fortunately,nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury.Compared with traditional drugs,nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’size,shape,and material characteristics.In this review,the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed.Furthermore,we summarized the applications of ROS-based nanoparticles,highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.展开更多
The objective of present study was to investigate the antioxidative and cardioprotective effects of polyphenol extracts from sea buckthorn (PESB) against myocardial ischemia reperfusion injury (MIRI). PESB was analyze...The objective of present study was to investigate the antioxidative and cardioprotective effects of polyphenol extracts from sea buckthorn (PESB) against myocardial ischemia reperfusion injury (MIRI). PESB was analyzed using HPLC-DAD and their antioxidant activities were evaluated by measuring the intrinsic free radicals cavenging capacity and inhibiting the formation of hydroxyl radical capacity. Experiments on the isolated rat hearts were carried out according to the improved Langendorff retrograde perfusion technology. Coronary effluent of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) activities were analyzed to determine the extent of myocardial injury. Protein expression levels of Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) I and II were measured to evaluate the degree of autophagy. In conclusion, coupled results from both in vivo and in vitro experiments have confirmed that PESB has potential health implications in both prevention and amelioration of MIRI, which may be attributed to the inhibition of autophagy.展开更多
Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effec...Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effects and mechanisms of betulin.展开更多
Objective:To explore the effects of electroacupuncture pretreatment on mitochondrial energy metabolism in the rats with myocardial ischemia reperfusion injury(MIRI).Methods:A total of 60 SPF Wistar rats were randomly ...Objective:To explore the effects of electroacupuncture pretreatment on mitochondrial energy metabolism in the rats with myocardial ischemia reperfusion injury(MIRI).Methods:A total of 60 SPF Wistar rats were randomly divided into a sham-operation group(sham group),a myocardial ischemia reperfusion injury group(MIRI group)and an electroacupuncture pretreatment group(EA group),20 rats in each one.The rats in the sham group and the MIRI group were binded for 7 days,once a day,20 min each time.On the 8th day,the sample was collected after the heart exposed for 50 min in thoractomy in the sham group and the sample was collected after ischemia for 20 min and reperfusion for 30 min in thoractomy in the MIRI group.In the EA group,the pretreatment intervention with electroacupuncture was applied at"Neiguan(内关PC6)","Guanyuan(关元CV4)"and"Zusanli(足三里ST36)"in the rats for 7 days,once a day,20 min each time.On the 8th day,after ischemia for 20 min and reperfusion for 30 min in thoractomy,the sample was collected in the EA group.The changes in STⅡsegment of electroacardiogram(ECG)were observed and measured.Using enzymelinked immunosorbent assay(ELISA),the concentrations of cardiac troponin T(cTnT)and cardiac troponin I(cTnl)were detected.Using nitro blue tetrazolium chloride monohydrate(NBT)staining,the myocardial infarction weight percentage was measured.Using ELISA,the concentrations of mitochondrial adenosine monophosphate(AMP),adenosine diphosphate(ADP)and adenosine triphosphate(ATP)were detected.Results:(1)STⅡchanges:in 20 min of ligation,compared with the sham group,the STⅡsegment of electrocardiograph(ECG)was elevated significantly in the MIRI group and EA group(both P<0.01),but the elevation range in the EA group was lower than that of the MIRI group(P<0.01).After reperfusion for30 min,the STⅡsegment was fallen by over 50%in the MIRI group and the EA group.Simultaneously,the STⅡsegment in the EA group was lower than that of the MIRI group(P<0.01).(2)Regarding myocardial infarction weight percentage,compared with the sham group,the infarction weight was larger in the MIRI group and the EA group(both P<0.05)and the infarction weight in the EA group was lower than that of the MIRI group(P<0.05).(3)Regarding the levels of serum cTnt and cTnI,compared with the sham group,the levels of serum cTnT and cTnI were higher in the MIRI group and the EA group(all P<0.01)and the levels of cTnT and cTnI in the EA group were lower than that of the MIRI group(both P<0.01).(4)Regarding the concentrations of AMP,ADP and ATP,compared with the sham group,ATP concentration was lower in the MIRI group and the EA group(both P<0.01)and the concentrations of AMP and ADP were higher(P<0.05,P<0.01).Compared with the MIRI group,ATP concentration was higher in the EA group(P<0.05)and the concentrations of AMP and ADP were lower(both P<0.01).Conclusions:Electroacupuncture pretreatment reduces the elevation of ECG STⅡsegment,decreases the concentrations of myocardial injury markers,cTnT and cTnI and regulates the transfer among AMP,ATP and ADP.The protective effect of electroacupuncture pretreatment may result from the regulation of mitochondrial energy metabolism.展开更多
Background When patients suffering with ST-segment elevation myocardial infarction(STEMI) undergo an percutaneous coronary intervention(PCI) and open the infarct-related coronary artery(IRCA), a myocardial ischemia re...Background When patients suffering with ST-segment elevation myocardial infarction(STEMI) undergo an percutaneous coronary intervention(PCI) and open the infarct-related coronary artery(IRCA), a myocardial ischemia reperfusion injury(MIRI) will occur. This leads to severe complications, such as an enlarged myocardial infarction area, reperfusion arrhythmia, and heart failure. Finding ways to mitigate the effects of MIRIs is therefore important. Our study aims to observe the effect and significance of the gradual ischemic postconditioning(IPOC)treatment on MIRI and autonomic nerves system(ANS) in patients with STEMI during PCIs. Methods We took the 121 patients diagnosed with STEMI that had been hospitalized in the cardiology department of our hospital from March 2019 to September 2020, and divided them into a control group(60 cases) and treatment group(61 cases). The control group received conventional PCI treatment, and the treatment group received gradual IPOC treatment. Results The gradual IPOC group was shown to achieve significantly better results than the control group(P<0.01) in the following: reduction of the incidence rate of arrhythmia cases during PCI, increase in proportion of ST-segment resolution at 24 hours after PCI, suppression of the postoperative overexcitement of the sympathetic and vagus nerve systems, recovery of the cardiac autonomic nerve function, reduction of c Tn T, NT-pro BNP and hs-CRP concentrations, and improvement of LVEF value. Conclusion During emergency PCIs for patients with STEMI, the operation of an gradual IPOC can lessen the myocardial infarction area, reduce inflammation, improve heart function, reduce reperfusion arrhythmia, and promote the recovery of cardiac autonomic nerve function, thereby reduce MIRI and benefitting patients.展开更多
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Fund of Dean of Huachuang Institute of Areca Research-Hainan(HCBL2020YZ-012)。
文摘The morbidity and mortality of cardiovascular diseases are very high,which has attracted more and more attention all over the world.Common treatment methods for clinical treatment of acute myocardial infarction include direct percutaneous coronary intervention and coronary artery bypass grafting,which can quickly restore blocked coronary blood flow and reduce the infarct size.However,the inevitable ischemia/reperfusion injury will occur during the recovery of coronary blood flow,its pathological mechanism is complicated,and the Western medicine countermeasures are very limited.Among the current drugs for the treatment of cardiovascular diseases,traditional Chinese medicine has become a research hotspot due to its multiple targets,safety,and low side effects.Ginger is the fresh rhizome of Zingiber officinale Rosc.,a perennial herbaceous plant in the ginger family.It is a dual-purpose resource of medicine and food.Ginger has the functions of relieving the appearance and dispelling cold,warming up and relieving vomiting,resolving phlegm and relieving cough,and relieving fish and crab poison.The chemical components of ginger mainly include volatile oil,gingerol,diphenylheptane,etc..Among them,6-gingerol,as the main active component of gingerols,has obvious pharmacological effects in myocardial protection,anti-oxidation,anti-inflammatory,etc..Studies have shown that 6-gingerol protects myocardium mainly through anti-oxidative stress,anti-inflammatory,inhibiting cell apoptosis,and preventing calcium influx.①Anti-oxidative stress:oxidative stress is a state where oxidation and anti-oxidation in the body are out of balance,and it is also an important factor leading to myocardial damage.Many studies have confirmed that 6-gingerol has an antioxidant effect,and it is considered a natural antioxidant.6-gingerol can significantly reduce the degree of oxidative stress and the level of reactive oxygen species caused by cardiomyocyte damage,and has a significant cardioprotective effect.②Anti-inflammatory:inflammation can cause substantial cell damage and organ dysfunction,which is another important cause of myocardial damage.6-gingerol can reduce the levels of inflammatory factors such as interleukin-6,interleukin-1β,and tumor necrosis factor-αin cardiomyocytes,and at the same time inhibit the TLR4/NF-κB signaling pathway,an important regulatory pathway of inflammation,showing that it may improve myocardial damage through anti-inflammatory effects.③Inhibition of apoptosis:apoptosis is a complex and orderly process in the autonomous biochemical process of cells,and one of the main mechanisms of myocardial injury.This process can be roughly divided into three pathways:mitochondria,endoplasmic reticulum,and death receptors.Among them,the mitochondrial pathway plays an important role,and Bcl-2 and Bax located upstream of this pathway can regulate the entire process of cell apoptosis by regulating the permeability of the mitochondrial membrane.Studies have found that the preventive application of 6-gingerol can reduce cell damage,reduce the number of apoptotic cells,reduce the activity of Bax and caspase-3,and increase the expression of Bcl-2.Therefore,6-gingerol pretreatment can reduce the damage of cardiomyocytes,and its mechanism may be related to the inhibition of apoptosis.④Prevent calcium influx:calcium overload is involved in the pathogenesis of myocardial ischemic injury,which may be related to excessive contracture,arrhythmia,and mitochondrial Ca2+accumulation that impairs myocardial function.6-gingerol inhibits the increase of intracellular Ca2+concentration by inhibiting L-type calcium current,thereby reducing extracellular Ca2+influx,thereby avoiding calcium overload and playing a cardioprotective effect.In summary,6-gingerol can effectively treat and improve myocardial ischemia/reperfusion injury,and it has great development potential in the fields of medicine and health products.
基金Construction Project of Traditional Chinese Medicine Academic Genre Inheritance Studio of the State Administration of Traditional Chinese Medicine(No.LPGZS2012-14)Construction Project of National Famous and old Traditional Chinese Medicine Expert Inheritance Studio of the State Administration of Traditional Chinese Medicine。
文摘Objective:To observe the protective effect of hesperidin on myocardial ischemia/reperfusion injury in type 2 diabetes mellitus and its effect on SIRT1/Nrf2/HO-1 signaling pathway.Methods:50 Sprague-Dawley(SD)rats were randomly assigned to the normal control group(NC),model group,ischemia-reperfusion group(IR),hesperidin group,SIRT1 inhibitor group and hesperidin plus SIRT1 inhibitor group.In addition to NC,the rats in the remaining groups were replicated by intraperitoneal of high-fat diet combined with injection of streptozotocin for type 2 diabetic rats.After then,the myocardial ischemia/reperfusion injury(MIRI)rat model was established by LAd for 30 minutes with 2 hours reperfusion.He staining was used to observe the pathological changes of myocardial tissue,and the levels of serum LDH,CK-MB and SOD,GSH and MDA in myocardial tissue were detected by kit methods,and the expression abundance of related proteins in 4-HNE and SIRT1/Nrf2/HO-1 signal pathway were detected by immunohistochemistry and Western blot;Results:Hesperidin could significantly inhibit cardiomyocyte necrosis and inflammatory cell infiltration,reduce LDH activity,CK-MB and MDA level,and increase SOD activity,GSH and 4-HNE level,the differences were statistically significant when compared with IR group(P<0.01).In addition,compared with the ischemia-reperfusion group,the expressions of SIRT1,Nrf2 and HO-1 proteins in hesperidin group were significantly up-regulated,the differences were statistically significant(P<0.01);Conclusion:Hesperidin inhibits oxidative stress by activating SIRT1/Nrf2/HO-1 signaling pathway,and play a protective effect of myocardial ischemia reperfusion injury in diabetic rats.
基金Supported by the Beijing University of Chinese Medicine Research and Innovation Team Project(No.2019-JYB-TD-08)Youth Science Fund Project of National Natural Science Foundation of China(No.81803906)。
文摘Mitophagy is one of the important targets for the prevention and treatment of myocardial ischemia/reperfusion injury(MIRI).Moderate mitophagy can remove damaged mitochondria,inhibit excessive reactive oxygen species accumulation,and protect mitochondria from damage.However,excessive enhancement of mitophagy greatly reduces adenosine triphosphate production and energy supply for cell survival,and aggravates cell death.How dysfunctional mitochondria are selectively recognized and engulfed is related to the interaction of adaptors on the mitochondrial membrane,which mainly include phosphatase and tensin homolog deleted on chromosome ten(PTEN)-induced kinase 1/Parkin,hypoxia-inducible factor-1α/Bcl-2 and adenovirus e1b19k Da interacting protein 3,FUN-14 domain containing protein 1 receptor-mediated mitophagy pathway and so on.In this review,the authors briefly summarize the main pathways currently studied on mitophagy and the relationship between mitophagy and MIRI,and incorporate and analyze research data on prevention and treatment of MIRI with Chinese medicine,thereby provide relevant theoretical basis and treatment ideas for clinical prevention of MIRI.
基金supported by funding from the Anhui Natural Science Foundation of China(No.2008085MH239).
文摘Autophagy is an evolutionarily conserved process involved in the degradation of long-lived proteins and excessive or dysfunctional organelles. As a pivotal cellular response, autophagy has been extensively studied and is known to be involved in various diseases. Ferroptosis is a recently discovered form of regulated cell death characterized by iron overload, leading to the accumulation of lethal levels of lipid hydroperoxides. Recently, an increasing number of studies have revealed a link between autophagy and ferroptosis. Myocardial ischemia/reperfusion injury (MIRI) is an urgent dilemma after myocardial infarction recanalization, which is regulated by several cell death pathways, including autophagy and ferroptosis. However, the potential relationship between autophagy and ferroptosis in MIRI remains unexplored. In this study, we briefly review the mechanisms of autophagy and ferroptosis, including their roles in MIRI. Moreover, we provide an overview of the potential crosstalk in MIRI. Clarifying the relationship between different cell death pathways may provide new ideas for the treatment of MIRI in the future.
基金supported by the National Natural Science Foundation of China(Nos.82172076,52273144,and 52033006)111 project,Collaborative Innovation Center of Suzhou Nano Science&Technology,Joint International Research Laboratory of Carbon-Based Functional Materials and Devices,and Suzhou Key Laboratory of Nanotechnology and Biomedicine.
文摘MicroRNA-208a(miR-208a)plays critical roles in the severe fibrosis and heart failure post myocardial ischemia/reperfusion(IR)injury.MiR-208a inhibitor(mI)with complementary RNA sequence can silence the expression of miR-208a,while it is challenging to achieve efficient and myocardium-targeted delivery.Herein,biomimetic nanocomplexes(NCs)reversibly coated with red blood cell membrane(RM)were developed for the myocardial delivery of mI.To construct the NCs,membrane-penetrating helical polypeptide(PG)was first adopted to condense mI and form the cationic inner core,which subsequently adsorbed catalase(CAT)via electrostatic interaction followed by surface coating with RM.The membrane-coated NCs enabled prolonged blood circulation after systemic administration,and could accumulate in the injured myocardium via passive targeting.In the oxidative microenvironment of injured myocardium,CAT decomposed H_(2)O_(2)to produce O_(2)bubbles,which drove the shedding of the outer RM to expose the positively charged inner core,thus facilitated effective internalization by cardiac cells.Based on the combined contribution of mI-mediated miR-208a silencing and CAT-mediated alleviation of oxidative stress,NCs effectively ameliorated the myocardial microenvironment,hence reducing the infarct size as well as fibrosis and promoting recovery of cardiac functions.This study provides an effective strategy for the cytosolic delivery of nucleic acid cargoes in the myocardium,and it renders an enlightened approach to resolve the blood circulation/cell internalization dilemma of cell membrane-coated delivery systems.
基金Supported by the National Natural Science Foundation of China(No.81970722)。
文摘Objective:To examine the effect of Shenmai Injection(SMJ)on ferroptosis during myocardial ischemia reperfusion(I/R)injury in rats and the underlying mechanism.Methods:A total of 120SPF-grade adult male SD rats,weighing 220–250 g were randomly divided into different groups according to a random number table.Myocardial I/R model was established by occluding the left anterior descending artery for 30 min followed by 120 min of reperfusion.SMJ was injected intraperitoneally at the onset of 120 min of reperfusion,and erastin(an agonist of ferroptosis),ferrostatin-1(Fer-1,an inhibitor of ferroptosis)and ML385(an inhibitor of nuclear factor erythroid-2 related factor 2(Nrf2))were administered intraperitoneally separately 30 min before myocardial ischemia as different pretreatments.Cardiac function before ischemia,after ischemia and after reperfusion was analysed.Pathological changes in the myocardium and the ultrastructure of cardiomyocytes were observed,and the myocardial infarction area was measured.Additionally,the concentration of Fein heart tissues and the levels of creatine kinase-MB(CK-MB),troponin I(cTnI),malondialdehyde(MDA)and superoxide dismutase(SOD)in serum were measured using assay kits,and the expressions of Nrf2,glutathione peroxidase 4(GPX4)and acyl-CoA synthetase long-chain family member 4(ACSL4)were examined by Western blot.Results:Compared with the sham group,I/R significantly injured heart tissues,as evidenced by the disordered,ruptured and oedematous myocardial fibres;the increases in infarct size,serum CK-MB,cTnI and MDA levels,and myocardial Feconcentrations;and the decreases in SOD activity(P<0.05).These results were accompanied by ultrastructural alterations to the mitochondria,increased expression of ACSL4 and inhibited the activation of Nrf2/GPX4 signalling(P<0.05).Compared with the I/R group,pretreatment with 9 mL/kg SMJ and 2 mg/kg Fer-1 significantly reduced myocardial I/R injury,Feconcentrations and ACSL4 expression and attenuated mitochondrial impairment,while 14 mg/kg erastin exacerbated myocardial I/R injury(P<0.05).In addition,cardioprotection provided by 9 mL/kg SMJ was completely reversed by ML385,as evidenced by the increased myocardial infarct size,CK-MB,cTnI,MDA and Feconcentrations,and the decreased SOD activity(P<0.05).Conclusions:Ferroptosis is involved in myocardial I/R injury.Pretreatment with SMJ alleviated myocardial I/R injury by activating Nrf2/GPX4 signalling-mediated ferroptosis,thereby providing a strategy for the prevention and treatment of ischemic heart diseases.
基金funding support from the National Natural Science Foundation of China(No.52033006 and 51873142)Suzhou Science and Technology Development Project(No.SYS2019072) Science Foundation of China (No. 52033006 and 51873142)+1 种基金Suzhou Science and Technology Development Project (No.SYS2019072), Collaborative Innovation Center of Suzhou NanoScience & Technology, the 111 project, Suzhou Key Laboratory ofNanotechnology and BiomedicineJoint InternationalResearch Laboratory of Carbon-Based Functional Materials andDevices。
文摘Myocardial ischemia reperfusion(IR)injury is closely related to the overwhelming inflammation in the myocardium.Herein,cardiomyocyte-targeted nanotherapeutics were developed for the reactive oxygen species(ROS)-ultrasensitive co-delivery of dexamethasone(Dex)and RAGE small interfering RNA(siRAGE)to attenuate myocardial inflammation.PPTP,a ROSdegradable polycation based on PGE2-modified,PEGylated,ditellurium-crosslinked polyethylenimine(PEI)was developed to surface-decorate the Dex-encapsulated mesoporous silica nanoparticles(MSNs),which simultaneously condensed siRAGE and gated the MSNs to prevent the Dex pre-leakage.Upon intravenous injection to IR-injured rats,the nanotherapeutics could be efficiently transported into the inflamed cardiomyocytes via PGE2-assisted recognition of over-expressed E-series of prostaglandin(EP)receptors on the cell membranes.Intracellularly,the over-produced ROS degraded PPTP into small segments,promoting the release of siRAGE and Dex to mediate effective RAGE silencing(72%)and cooperative antiinflammatory effect.As a consequence,the nanotherapeutics notably suppressed the myocardial fibrosis and apoptosis,ultimately recovering the systolic function.Therefore,the current nanotherapeutics represent an effective example for the codelivery and on-demand release of nucleic acid and chemodrug payloads,and might find promising utilities toward the synergistic management of myocardial inflammation.
基金Supported by the National Natural Science Foundation of China(No.81473471 and No.81603429)Foundation of Guangdong Hospital of Chinese Medicine(No.YK2013B2N11,No.YN2014ZH01,No.YN2014ZHR203,and No.YN2016QJ19)。
文摘Objective:To study the protective mechanism of Chinese medicine Suxiao Jiuxin Pills(速效救心丸,SXJ)on myocardial ischemia and reperfusion(I/R)injury.Methods:Mouse myocardial I/R injury model was created by 30-min coronary artery occlusion followed by 24-h reperfusion,the mice were then divided into the sham group(n=7),the I/R group(n=13),the tirofiban group(TIR,positive drug treatment,n=9),and the SXJ group(n=11).Infarct size(IS),risk region(RR),and left ventricle(LV)were analyzed with double staining methods.In addition,H9C2 rat cardiomyocytes were cultured with Na2S2O4 to simulate I/R in vitro.The phosphorylation of extracellular regulated protein kinases1/2(ERK1/2),protein kinase B(AKT),glycogen synthase kinase-3β(GSK3β),and protein expression of GATA4 in nucleus were detected with Western blot assay.Results:The ratio of IS/RR in SXJ and TIR groups were lower than that in I/R group(SXJ,22.4%±6.6%;TIR,20.8%±3.3%;vs.I/R,35.4%±3.7%,P<0.05,respectively).In vitro experiments showed that SXJ increased the Na2S2O4-enhanced phosphorylation of AKT/GSK3βand nuclear expression of GATA4.Conclusion:SXJ prevents myocardial I/R injury in mice by activating AKT/GSK3βand GATA4 signaling pathways.
文摘Background Myocardial ischemia/reperfusion injury(MI/RI)during myocardial infarction worsens outcomes. It has been proved that ginsenoside Rb1 has a great impact on ischemia/reperfusion(I/R)injury. The aim of this study is to explore the protective effect of the pretreatment with ginsenoside Rb1 on MI/RI and investigate the underlying mechanisms about the preventive action. Methods A total of 27 healthy adult Sprague-Dawley(SD)rats were randomly divided into 3 groups(n=9 per group):A sham-operated group(Sham n=9);an ischemia 40 min/reperfusion 2 h(I/R n=9)of the cardiac muscle group;Rb1-treated group was divided into 3 subgroups(Rb1 10 mg/kg,20 mg/kg,40 mg/kg,n=3). Ginsenosides Rb1 at different concentrations were injected intraperitoneally for 3 days continuously before ligation. A model of MI/RI was constructed by ligation of the left coronary artery anterior descending branch in rats. Myocardial infarction area after I/R was measured bytriphenyltetrazolium chloride(TTC)staining of myocardial tissue. Hematoxylin and eosin(HE)staining and electrocardiogram indication were used to observe myocardial cell injury and ischemia,respectively. The expression of caspase-8 protein was observed by immunohistochemistry staining. Results The pretreatment of 40 mg/kg dose of ginsenoside Rb1 could decrease the expression of caspase-8 protein caused by I/R and the apoptosis of myocardial cells,improve myocardial ischemia,reduce the area of myocardial infarction and ameliorate MI/RI.Conclusions These results demonstrate that ginsenoside Rb1 has a significant protective effect on MI/RI through attenuating the apoptosis of myocardial cells and improving myocardial ischemia at appropriate dose,which provides new insights into the potential therapy of MI/RI.
文摘Background The most effective treatment for Acute myocardial infarction(AMI)is timely and effective reperfusion therapy;however,the process of reperfusion therapy can worsen the myocardial damage.This pathological process is known as myocardial ischemia-reperfusion injury(I/R).But,the mechanism of I/R is not fully understood and there is no available effective treatment for I/R.This article will review the mechanisms of occurrence and treatments currently found for I/R.
基金This work was supported by the National Natural Science Foundation of China,China(No.21974134,81974508,81673492,81873581)Innovation-Driven Project of Central South University(No.202045005)+1 种基金Special Science and Technology Plan of Changsha City.(No.kq2001048)Key Research Project of Ningxia Hui Autonomous Region(Major Project)(2021BEG01001).
文摘Interventional coronary reperfusion strategies are widely adopted to treat acute myocardial infarction,but morbidity and mortality of acute myocardial infarction are still high.Reperfusion injuries are inevitable due to the generation of reactive oxygen species(ROS)and apoptosis of cardiac muscle cells.However,many antioxidant and anti-inflammatory drugs are largely limited by pharmacokinetics and route of administration,such as short half-life,low stability,low bioavailability,and side effects for treatment myocardial ischemia reperfusion injury.Therefore,it is necessary to develop effective drugs and technologies to address this issue.Fortunately,nanotherapies have demonstrated great opportunities for treating myocardial ischemia reperfusion injury.Compared with traditional drugs,nanodrugs can effectively increase the therapeutic effect and reduces side effects by improving pharmacokinetic and pharmacodynamic properties due to nanodrugs’size,shape,and material characteristics.In this review,the biology of ROS and molecular mechanisms of myocardial ischemia reperfusion injury are discussed.Furthermore,we summarized the applications of ROS-based nanoparticles,highlighting the latest achievements of nanotechnology researches for the treatment of myocardial ischemia reperfusion injury.
文摘The objective of present study was to investigate the antioxidative and cardioprotective effects of polyphenol extracts from sea buckthorn (PESB) against myocardial ischemia reperfusion injury (MIRI). PESB was analyzed using HPLC-DAD and their antioxidant activities were evaluated by measuring the intrinsic free radicals cavenging capacity and inhibiting the formation of hydroxyl radical capacity. Experiments on the isolated rat hearts were carried out according to the improved Langendorff retrograde perfusion technology. Coronary effluent of lactate dehydrogenase (LDH) and creatine kinase isoenzyme (CK-MB) activities were analyzed to determine the extent of myocardial injury. Protein expression levels of Beclin-1, microtubule-associated protein 1 light chain 3 (LC3) I and II were measured to evaluate the degree of autophagy. In conclusion, coupled results from both in vivo and in vitro experiments have confirmed that PESB has potential health implications in both prevention and amelioration of MIRI, which may be attributed to the inhibition of autophagy.
基金Supported by Talent Training Project of the Central Support Fund for the Reform and Development of Local Colleges and Universities(2020GSP16)。
文摘Betulin is main component of triterpenoids in bark extract of Betula platyphylla,and has antibacterial,antiviral,liver protecting,cholagogic,antitumorus and other functions.This paper reviews the pharmacological effects and mechanisms of betulin.
基金Supported by National Natural Science Foundation of China Youth Program:81704142Hubei Science and Technology Plan Project:2018CFC890+7 种基金The Twelfth Batch of Self-Selected Research Projects(“Collaborative Innovation”Special Fund):YZ-1845Qihuang Project of National Administration of Traditional Chinese Medicine(National Administration of Traditional Chinese Medicine Yard[2018]:284)Hubei Chinese Medicine Teacher Project(Bulletin of Hubei Health and Family Planning Commission[2018]:15)Hubei Hospital of Traditional Chinese Medicine,the First Tanhualin Famous Doctor,Student Training ProjectHubei Administration of Traditional Chinese Medicine[2018]No.72Wuhan Young and Middle-aged Medical Backbone Talents(Sixth Batch)No.116Family Planning Tong[2018]Young Elite Scientist Sponsors Hip Program by CAST:No.2017QNRC001。
文摘Objective:To explore the effects of electroacupuncture pretreatment on mitochondrial energy metabolism in the rats with myocardial ischemia reperfusion injury(MIRI).Methods:A total of 60 SPF Wistar rats were randomly divided into a sham-operation group(sham group),a myocardial ischemia reperfusion injury group(MIRI group)and an electroacupuncture pretreatment group(EA group),20 rats in each one.The rats in the sham group and the MIRI group were binded for 7 days,once a day,20 min each time.On the 8th day,the sample was collected after the heart exposed for 50 min in thoractomy in the sham group and the sample was collected after ischemia for 20 min and reperfusion for 30 min in thoractomy in the MIRI group.In the EA group,the pretreatment intervention with electroacupuncture was applied at"Neiguan(内关PC6)","Guanyuan(关元CV4)"and"Zusanli(足三里ST36)"in the rats for 7 days,once a day,20 min each time.On the 8th day,after ischemia for 20 min and reperfusion for 30 min in thoractomy,the sample was collected in the EA group.The changes in STⅡsegment of electroacardiogram(ECG)were observed and measured.Using enzymelinked immunosorbent assay(ELISA),the concentrations of cardiac troponin T(cTnT)and cardiac troponin I(cTnl)were detected.Using nitro blue tetrazolium chloride monohydrate(NBT)staining,the myocardial infarction weight percentage was measured.Using ELISA,the concentrations of mitochondrial adenosine monophosphate(AMP),adenosine diphosphate(ADP)and adenosine triphosphate(ATP)were detected.Results:(1)STⅡchanges:in 20 min of ligation,compared with the sham group,the STⅡsegment of electrocardiograph(ECG)was elevated significantly in the MIRI group and EA group(both P<0.01),but the elevation range in the EA group was lower than that of the MIRI group(P<0.01).After reperfusion for30 min,the STⅡsegment was fallen by over 50%in the MIRI group and the EA group.Simultaneously,the STⅡsegment in the EA group was lower than that of the MIRI group(P<0.01).(2)Regarding myocardial infarction weight percentage,compared with the sham group,the infarction weight was larger in the MIRI group and the EA group(both P<0.05)and the infarction weight in the EA group was lower than that of the MIRI group(P<0.05).(3)Regarding the levels of serum cTnt and cTnI,compared with the sham group,the levels of serum cTnT and cTnI were higher in the MIRI group and the EA group(all P<0.01)and the levels of cTnT and cTnI in the EA group were lower than that of the MIRI group(both P<0.01).(4)Regarding the concentrations of AMP,ADP and ATP,compared with the sham group,ATP concentration was lower in the MIRI group and the EA group(both P<0.01)and the concentrations of AMP and ADP were higher(P<0.05,P<0.01).Compared with the MIRI group,ATP concentration was higher in the EA group(P<0.05)and the concentrations of AMP and ADP were lower(both P<0.01).Conclusions:Electroacupuncture pretreatment reduces the elevation of ECG STⅡsegment,decreases the concentrations of myocardial injury markers,cTnT and cTnI and regulates the transfer among AMP,ATP and ADP.The protective effect of electroacupuncture pretreatment may result from the regulation of mitochondrial energy metabolism.
基金supported by Foundation Project of Qingdao Medical Research Guidance Plan (No.2020-WJZD095)。
文摘Background When patients suffering with ST-segment elevation myocardial infarction(STEMI) undergo an percutaneous coronary intervention(PCI) and open the infarct-related coronary artery(IRCA), a myocardial ischemia reperfusion injury(MIRI) will occur. This leads to severe complications, such as an enlarged myocardial infarction area, reperfusion arrhythmia, and heart failure. Finding ways to mitigate the effects of MIRIs is therefore important. Our study aims to observe the effect and significance of the gradual ischemic postconditioning(IPOC)treatment on MIRI and autonomic nerves system(ANS) in patients with STEMI during PCIs. Methods We took the 121 patients diagnosed with STEMI that had been hospitalized in the cardiology department of our hospital from March 2019 to September 2020, and divided them into a control group(60 cases) and treatment group(61 cases). The control group received conventional PCI treatment, and the treatment group received gradual IPOC treatment. Results The gradual IPOC group was shown to achieve significantly better results than the control group(P<0.01) in the following: reduction of the incidence rate of arrhythmia cases during PCI, increase in proportion of ST-segment resolution at 24 hours after PCI, suppression of the postoperative overexcitement of the sympathetic and vagus nerve systems, recovery of the cardiac autonomic nerve function, reduction of c Tn T, NT-pro BNP and hs-CRP concentrations, and improvement of LVEF value. Conclusion During emergency PCIs for patients with STEMI, the operation of an gradual IPOC can lessen the myocardial infarction area, reduce inflammation, improve heart function, reduce reperfusion arrhythmia, and promote the recovery of cardiac autonomic nerve function, thereby reduce MIRI and benefitting patients.
