Objective: To investigate the protective effect of nitrates postconditioning on myocardial ischemia-reperfusion injury and whether it plays a regulatory role in TNF-α in patients with STEMI during PCI. Methods: Patie...Objective: To investigate the protective effect of nitrates postconditioning on myocardial ischemia-reperfusion injury and whether it plays a regulatory role in TNF-α in patients with STEMI during PCI. Methods: Patients with STEMI who underwent PCI were selected, except for obvious anemia, head trauma, cerebral hemorrhage, hypotension (systolic blood pressure less than 90 mmHg), and patients with autoimmune diseases, all kinds of acute and chronic infections and malignant tumors. They were randomly divided into PCI standardized treatment group and isosorbide dinitrate postconditioning during PCI group. The concentrations of cTnI and TNF-α in serum were detected by ELISA method in each group before PCI and after 2 hours, 1 day, 4 days and 7 days of PCI. Results: 1) There were no statistically significant differences in sex, age, smoking history, diabetes, hypertension and blood lipid abnormality in two groups. 2) Before operation, the concentration of cTnI in two groups was not statistically significant. The concentration of cTnI in the experimental group was lower than that of the control group after 4 days and 7 days of PCI, and P α in two groups before operation. The concentration of TNF-α in the experimental group was lower than that in the control group after 1 day, 4 days and 7 days of PCI, and P α in two groups was both in 1 day after operation, and the peak level of the experimental group and the level of each time after the operation were lower than that of the control group. Conclusion: Nitrates postconditioning during PCI in patients with STEMI has a protective effect on myocardial ischemia-reperfusion injury. Nitrates postconditioning has an effect to reduce the level of TNF-α of patients with STEMI after PCI treatment, and may have the mechanism of alleviating the inflammatory response after myocardial ischemia and reperfusion.展开更多
BACKGROUND:Ischemia-reperfusion injury occurs when ischemic tissues or organs suffer from further functional and structural damage when their blood supply recovers.This study aimed to contrast the protective effects o...BACKGROUND:Ischemia-reperfusion injury occurs when ischemic tissues or organs suffer from further functional and structural damage when their blood supply recovers.This study aimed to contrast the protective effects of ischemic preconditioning and ischemic postconditioning in hepatic ischemia-reperfusion injury in rats.METHODS:Thirty-two healthy male Wistar rats were randomly divided into four groups:sham-operated(SO),ischemia-reperfusion(IR),ischemic preconditioning(I-pre),and ischemic postconditioning(I-post).Blood samples and hepatic tissue were taken from all groups after the experiments.RESULTS:There were significant differences between the IR,I-pre and I-post groups in alanine aminotransferase and aspartate aminotransferase levels,NF-κB p65 expression,apoptosis index and superoxide dismutase activity in hepatic tissue.There were no significant differences between the I-pre and I-post groups.CONCLUSIONS:Ischemic postconditioning and ischemic preconditioning reduce hepatic ischemia-reperfusion injury,but in clinical practice the former is a more appropriate choice.展开更多
Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotect...Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.展开更多
During acute reperfusion,the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes.However,whether long noncoding RNAs are involved in neuroprotective effects foll...During acute reperfusion,the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes.However,whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear.In this study,RNA isolation and library preparation was performed for long noncoding RNA sequencing,followed by determining the coding potential of identified long noncoding RNAs and target gene prediction.Differential expression analysis,long noncoding RNA functional enrichment analysis,and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats.Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery.Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke.The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke.The predicted target genes of some of the identified long noncoding RNAs(cis targets)were related to the cellular response to ischemia and stress,cytokine signal transduction,inflammation,and apoptosis signal transduction pathways.In addition,15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning.Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis.Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction.These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke.The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University(approval No.KMMU2018018)in January 2018.展开更多
AIM:To investigate the protective effects of remote ischemic postconditioning(RIP)against limb ischemiareperfusion(IR)-induced gastric mucosal injury.METHODS:Gastric IR was established in male Wistar rats by placing a...AIM:To investigate the protective effects of remote ischemic postconditioning(RIP)against limb ischemiareperfusion(IR)-induced gastric mucosal injury.METHODS:Gastric IR was established in male Wistar rats by placing an elastic rubber band under a pressure of 290-310 mmHg on the proximal part of both lower limbs for 3 h followed by reperfusion for 0,1,3,6,12or 24 h.RIP was performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of the femoral aortic immediately after IR and before reperfusion for up to 24 h.Rats were randomly assigned to receive IR(n=36),IR followed by RIP(n=36),or sham treatment(n=36).Gastric tissue samples were collected from six animals in each group at each timepoint and processed to determine levels of malondialdehyde(MDA),superoxide dismutase(SOD),xanthine oxidase(XOD)and myeloperoxidase(MPO).Additional samples were processed for histologic analysis by hematoxylin and eosin staining.Blood samples were similarly collected to determine serum levels of lactate dehydrogenase(LDH),creatine kinase(CK),tumor necrosis factor(TNF)-αand interleukin(IL)-10.RESULTS:The pathologic changes in gastric tissue induced by IR were observed by light microscopy.Administration of RIP dramatically reduced the gastric damage score after 6 h of reperfusion(5.85±0.22 vs7.72±0.43;P<0.01).In addition,RIP treatment decreased the serum activities of LDH(3.31±0.32 vs 6.46±0.03;P<0.01),CK(1.94±0.20 vs 4.54±0.19;P<0.01)and the concentration of TNF-α(53.82±0.85vs 88.50±3.08;P<0.01),and elevated the concentration of IL-10(101.46±5.08 vs 99.77±4.32;P<0.01)induced by IR at 6 h.Furthermore,RIP treatment prevented the marked elevation in MDA(3.79±0.29vs 6.39±0.81)content,XOD(7.81±0.75 vs 10.37±2.47)and MPO(0.47±0.05 vs 0.82±0.03)activities,and decrease in SOD(4.95±0.32 vs 3.41±0.38;P<0.01)activity in the gastric tissue as measured at 6 h.CONCLUSION:RIP provides effective functional protection and prevents cell injury to gastric tissue induced by limb IR via anti-inflammatory and antioxidant actions.展开更多
This study examined the protective effect of ischemic postconditioning(IPoC) and minocycline postconditioning(MT) on myocardial ischemia-reperfusion(I/R) injury in atherosclerosis(AS) animals and the possible mechanis...This study examined the protective effect of ischemic postconditioning(IPoC) and minocycline postconditioning(MT) on myocardial ischemia-reperfusion(I/R) injury in atherosclerosis(AS) animals and the possible mechanism.Forty male healthy rabbits were injected with bovine serum albumin following feeding on a high fat diet for 6 weeks to establish AS model.AS rabbits were randomly divided into 3 groups:(1) I/R group,the rabbits were subjected to myocardial ischemia for 35 min and then reperfusion for 12 h;(2) IPoC group,the myocardial ischemia lasted for 35 min,and then reperfusion for 20 s and ischemia for 20 s [a total of 3 cycles(R20s/I20s×3)],and then reperfusion was sustained for 12 h;(3) MT group,minocycline was intravenously injected 10 min before reperfusion.The blood lipids,malondialdehyde(MDA),superoxide dismutase(SOD),soluble cell adhesion molecule(sICAM),myeloperoxidase(MPO),and cardiac troponin T(cTnT) were biochemically determined.The myocardial infarction size(IS) and apoptosis index(AI) were measured by pathological examination.The expression of bcl-2 and caspase-3 was detected in the myocardial tissue by using reverse transcription-polymerase chain reaction(RT-PCR).The results showed that the AS models were successfully established.The myocardial IS,the plasma levels of MDA,sICAM,MPO and cTnT,and the enzymatic activity of MPO were significantly decreased,and the plasma SOD activity was significantly increased in IPoC group and MT group as compared with I/R group(P<0.05 for all).The myocardial AI and the caspase-3 mRNA expression were lower and the bcl-2 mRNA expression was higher in IPoC and MT groups than those in I/R group(all P<0.05).It is concluded that the IPoC and MT can effectively reduce the I/R injury in the AS rabbits,and the mechanisms involved anti-oxidation,anti-inflammation,up-regulation of bcl-2 expression and down-regulation of caspase-3 expression.Minocycline can be used as an effective pharmacologic postconditioning drug to protect myocardia from I/R injury.展开更多
Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual condi...Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable Post C protocols and investigate the potential protective mechanism.Methods: Thirty Sprague–Dawley rats were randomly divided into 3 groups: the sham group(n = 5),standard orthotopic liver transplantation group(OLT, n = 5), Post C group(OLT followed by clamping and re-opening the portal vein for different time intervals, n = 20). Post C group was then subdivided into 4 groups according to the different time intervals:(10 s × 3, 10 s × 6, 30 s × 3, 60 s × 3, n = 5 in each subgroup). Liver function, histopathology, malondialdehyde(MDA), myeloperoxidase(MPO), expressions of p-Akt and endoplasmic reticulum stress(ERS) related genes were evaluated.Results: Compared to the OLT group, the grafts subjected to Post C algorithm(without significant prolonging the total ischemic time) especially with short stimulus and more cycles(10 s × 6) showed significant alleviation of morphological damage and graft function. Besides, the production of reactive oxidative agents(MDA) and neutrophil infiltration(MPO) were significantly depressed by Post C algorithm. Most of ERS related genes were down-regulated by Post C(10 s × 6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.Conclusions: Post C algorithm, especially 10 s × 6 algorithm, showed to be effective against rat liver graft IRI. These protective effects may be associated with its antioxidant, inhibition of ERS and activation of p-Akt expression of reperfusion injury salvage kinase pathway.展开更多
Objective To investigate the effect of sevoflurane preconditioning and postconditioning on lung ischemia-reperfusion(IR) injury and apoptosis in rat.Methods Wistar rats were randomly assigned to four groups:sham group...Objective To investigate the effect of sevoflurane preconditioning and postconditioning on lung ischemia-reperfusion(IR) injury and apoptosis in rat.Methods Wistar rats were randomly assigned to four groups:sham group(n =6):no ischaemia-reperfusion;IR group(n =6):left lung ischemia was achieved by clamping the hilum for 90 min,followed by 120 min reperfusion;sev+pre group(n =6):1 minimum alveolar concentration(MAC) sevoflurane was admi-nistered for 30 min prior to ischemia;sev+post group(n =6):ischemia was followed by 1 MAC sevoflurane postconditioning at the first 30 min reperfusion.PaO2 was measured after reperfusion.The number of apoptotic cells was estimated using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling(TUNEL) technique.Results After ischemia-reperfusion,a significant deterioration of PaO2 was noticed and the number of apoptotic cells remarkably increased compared with that of sham group.In sev+pre group and sev+post group,PaO2 was(85.7±14.4) mmHg and(88.6±12.5) mmHg respectively,which was apparently increased compared with that in IR group [(63.9±11.3) mmHg,P <0.05].The number of apoptotic cells in sev+pre group [(6.94 ± 1.49)%] and sev+post group [(7.69 ± 1.61)%] was significantly lower than that in IR group [(12.12 ± 2.77)%,P <0.05].But all parameters showed no significant difference between sev+pre group and sev+post group.Conclusions Both sevoflurane preconditioning and postconditioning could prevent lung ischemia-reperfusion injury and attenuate apoptosis in rat.展开更多
Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprote...Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprotection efficacy of IP for IR.We established mouse models of IR and showed that compared to Sham group,IR group had obvious brain infract and neurological dysfunction.In IR+IP group,brain infract and neurological dysfunction improved compared to IR group.However,in IR+IP+RW group brain infract and neurological dysfunction improved much better.TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR.However,the number of apoptotic cells was significantly reduced in RW+IP group.In addition,the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group,while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group.Moreover,in IR+IP+RW group,MDA level was further decreased and SOD level was further increased compared to IR+IP group.Finally,both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice.In conclusion,RW combined with IP reduces brain infract and neurological dysfunction in mice after IR,and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.展开更多
Objective:To analyze the influences of locial ischemic postconditioning and remote limb ischemic postconditioning on oxidative stress response with myocardial ischemia reperfusion in rats.Methods:Thirty-two SD rats we...Objective:To analyze the influences of locial ischemic postconditioning and remote limb ischemic postconditioning on oxidative stress response with myocardial ischemia reperfusion in rats.Methods:Thirty-two SD rats were randomly divided into Sham group,ischemia/reperfusion(I/R)group,local ischemic postconditioning(LIPC)group,and remote limb ischemic postconditioning(RIPC)group,after 3 hourse reperfusion,the contents of serum creatinine kinase,MB isoenzyme(CK-MB),xanthine oxidase(XOD),superoxide dismutase(SOD),myeloperoxidase(MPO),tumor necrosis factor-α(TNF-α)were measured.The 2,3,5-triphenyltetrazolium chloride(TTC)staining was carried out to evaluate the area of myocardial infarction,cardiac function was evaluated by echocardiography,and HE staining was performed to observe the morphology of myocardial cells.Results:Compared with the Sham group,the SOD contents of the I/R group,LIPC group,RIPC group reduced significantly(P<0.05),the XOD,MPO,TNF-αcontents increased significantly(P<0.05);Compared with the I/R group,the TNF-αcontents of the LIPC group reduced significantly(P<0.05),other oxidative stress indicators of the LIPC group had no significant differences;Compared with the I/R group,the MPO and TNF-αcontents reduced(P<0.05),the SOD and XOD contents of the RIPC group had no significant differences;Compared with the LIPC group,the MPO contents reduced(P<0.05)in the RIPC group,other oxidative stress indicators had no significant differences.Compared with the Sham group,myocardial infarction area,CK-MB contents,LVIDs increased with the reduction of EF in I/R group,LIPC group,RIPC group(P<0.05),HE staining had differences;Compared with the I/R group,myocardial infarction area,CK-MB contents,LVIDd,LVIDs,EF and HE staining results had no significant differences in the LIPC group and the RIPC group;Compared with the RIPC group,the LIPC group had no significant differences.Conclusion:Remote limb ischemic postconditioning and local ischemic postconditioning can partially reduce the oxidative stress response,but does not significantly reduce myocardial infarction area,improve cardiac function.展开更多
Objectives To evaluate the effect of hydrogen sulfide(H2S) postconditioning on myocardial ischemia-reperfusion (I/R) by pressure-volume loop(P-V loop). Methods The I/R model of rat in vivo was established by ligating ...Objectives To evaluate the effect of hydrogen sulfide(H2S) postconditioning on myocardial ischemia-reperfusion (I/R) by pressure-volume loop(P-V loop). Methods The I/R model of rat in vivo was established by ligating the left anterior descending coronary artery for 30min and reperfusing for 120 min.Wistar rats(n=32) were ran- domly divided into 4 groups;Sham operation,ischemia-reperfusion (I/R),Ischemic postconditioning(IPO) and H2S postconditioning.In sham operation,there was no ligation.In IPO,at the start of reperfusion,three cycles of 30s reperfusion and 30s LAD reocclusion preceded the 3h of reperfusion. In H2S postconditioning,NaHS(15μmol/kg,Sodium hydrosulfide)was administrated before coronary artery reperfusion. The heart rate(HR),I/R arrhythmia,the left ventricular end-systolic pressure(LVESP),left ventricular enddiastolic pressure(LVEDP),the slope of the end- systolic P-V relation(ESPVR) and the slope of the end-diastolic P-V relation(EDPVR) were detected.Infarct size was determined by scanning the images of the rat heart ventricular sections stained with Evans blue and TTC.Results Compared with I/R group,the I/R arrhythmia and the infarct size were decreased significantly(PPP2S postconditioning group.Conclusions Myocardial I/R injury was decreased by H2S post-conditioning, and it was sensitive and accurate to evaluate the heart function by P-V loop.展开更多
Sevoflurane postconditioning reduces myocardial infarct size.The objective of this study was to examine the role of the phosphatidylinositol-3-kinase(PI3K)/Akt pathway in anesthetic postconditioning and to determine w...Sevoflurane postconditioning reduces myocardial infarct size.The objective of this study was to examine the role of the phosphatidylinositol-3-kinase(PI3K)/Akt pathway in anesthetic postconditioning and to determine whether PI3K/Akt signaling modulates the expression of pro-and antiapoptotic proteins in sevoflurane postconditioning.Isolated and perfused rat hearts were prepared first,and then randomly assigned to the following groups:Sham-operation(Sham),ischemia/reperfusion(Con),sevoflurane postconditioning(SPC),Sham plus 100 nmol/L wortmannin(Sham+Wort),Con+Wort,SPC+Wort,and Con+dimethylsulphoxide(DMSO).Sevoflurane postconditioning was induced by administration of sevoflurane(2.5%,v/v) for 10 min from the onset of reperfusion.Left ventricular developed pressure(LVDP),left ventricular end-diastolic pressure(LVEDP),maximum increase in rate of LVDP(+dP/dt),maximum decrease in rate of LVDP(?dP/dt),heart rate(HR),and coronary flow(CF) were measured at baseline,R30 min(30 min of reperfusion),R60 min,R90 min,and R120 min.Creatine kinase(CK) and lactate dehydrogenase(LDH) were measured after 5 min and 10 min reperfusion.Infarct size was determined by triphenyltetrazolium chloride staining at the end of reperfusion.Total Akt and phosphorylated Akt(phospho-Akt),Bax,Bcl-2,Bad,and phospho-Bad were determined by Western blot analysis.Analysis of variance(ANOVA) and Student-Newman-Keuls' test were used to investigate the significance of differences between groups.The LVDP,±dP/dt,and CF were higher and LVEDP was lower in the SPC group than in the Con group at all points of reperfusion(P<0.05).The SPC group had significantly reduced CK and LDH release and decreased infarct size compared with the Con group [(22.9±8)% vs.(42.4±9.4)%,respectively;P<0.05].The SPC group also had increased the expression of phospho-Akt,Bcl-2,and phospho-Bad,and decreased the expression of Bax.Wortmannin abolished the cardioprotection of sevoflurane postconditioning.Sevoflurane postconditioning may protect the isolated rat heart.Activation of PI3K and modulation of the expression of pro-and antiapoptotic proteins may play an important role in sevoflurane-induced myocardial protection.展开更多
Ischemic preconditioning and postconditioning distinctly attenuate ventricular arrhythmia after ischemia without affecting the severity of myocardial stunning. Therefore,we report the effects of sevoflurane preconditi...Ischemic preconditioning and postconditioning distinctly attenuate ventricular arrhythmia after ischemia without affecting the severity of myocardial stunning. Therefore,we report the effects of sevoflurane preconditioning and postconditioning on stunned myocardium in isolated rat hearts. Isolated rat hearts were underwent 20 min of global ischemia and 40 min of reperfusion. After an equilibration period (20 min),the hearts in the preconditioning group were exposed to sevoflurane for 5 min and next washout for 5 min before ischemia. Hearts in the sevoflurane postconditioning group underwent equilibration and ischemia,followed immediately by sevoflurane exposure for the first 5 min of reperfusion. The control group received no treatment before and after ischemia. Left ventricular pressure,heart rate,coronary flow,electrocardiogram,and tissue histology were measured as variables of ventricular function and cellular injury,respectively. There was no significant difference in the duration of reperfusion ventricular ar-rhythmias between control and sevoflurane preconditioning group (P=0.195). The duration of reperfusion ventricular arrhythmias in the sevoflurane postconditioning group was significantly shorter than that in the other two groups (P<0.05). ±(dP/dt)max in the sevoflurane preconditioning group at 5,10,15,20,and 30 min after reperfusion was sig-nificantly higher than that in the control group (P<0.05),and there were no significant differences at 40 min after reperfusion among the three groups (P>0.05). As expected,for a 20-min general ischemia,infarct size in heart slices determined by 2,3,5-triphenyltetrazolium chloride staining among the groups was not obvious. Sevoflurane postcon-ditioning reduces reperfusion arrhythmias without affecting the severity of myocardial stunning. In contrast,sevoflu-rane preconditioning has no beneficial effects on reperfusion arrhythmias,but it is in favor of improving ventricular function and recovering myocardial stunning. Sevoflurane preconditioning and postconditioning may be useful for correcting the stunned myocardium.展开更多
It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo.Our aim was to investigate the duration of effec...It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo.Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion(I/R) injury.Adult male Sprague-Dawley rats were randomly divided into six groups(n=12):a sham-operation group,an I/R group,and four sevoflurane postconditioning groups(S2,S5,S10,and S15).In the S2,S5,S10,and S15 groups,the duration times of sevoflurane administration were 2,5,10,and 15 min after the onset of reperfusion,respectively.The isolated rat hearts were mounted on the Langendorff system,and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion.Left ventricular(LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30,60,90,and 120 min of reperfusion were analyzed.Myocardial infarct size at the end of reperfusion(n=7 in each group) and the expression of myocardial phosphorylated Akt(p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts(n=5 in each group).Compared with the I/R group,the S5,S10,and S15 groups had significantly improved left ventricular end-diastolic pressure(LVEDP),left ventricular developed pressure(LVDP),and the maximal rate of rise or fall of the LV pressure(±dP/dtmax),and decreased myocardial infarct size(P<0.05),but not the S2 group.After 15 min of reperfusion,the expression of p-Akt was markedly up-regulated in the S5,S10,and S15 groups compared with that in the I/R group(P<0.05),but not in the S2 group.Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.展开更多
Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on cerebral edema and the AQP4 expression following HIBD and to verily t...Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on cerebral edema and the AQP4 expression following HIBD and to verily the neuroprotection of IPostC and the relationship between changes of AQP4 expression and cerebral edema.Methods:Water content was measured with dry-wet method,and AQP4 transcription and the protein expression of the lesions were detected with real-time PCR and immunohistochemistry staining,respectively.Results:Within 6-48 hours,the degree of ipsilateral cerebral edema was significantly lower in IPostC-15 s/15 s group than in HIBD group.Similar to the HIBD group,the AQP4 transcription and expression in the IPostC group showed a downward and then upward trend.But the expression was still more evident in the HIBD group than in the IPostC-15 s/15 s group.From 24 to 48 hours,IPostC-15 s/15 s decreased the slowing down expression of AQP4.Conclusion:IPostC has neuroprotective effect on neonatal rats with HIBD and it may relieve cerebral edema by regulating the expression of AQP4.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
BACKGROUND: Rapid and complete reperfusion has been widely adopted in the treatment of patients with acute myocardial infarction(AMI), but this process sometimes can cause severe reperfusion injury. This study aimed t...BACKGROUND: Rapid and complete reperfusion has been widely adopted in the treatment of patients with acute myocardial infarction(AMI), but this process sometimes can cause severe reperfusion injury. This study aimed to investigate different patterns of post-conditioning in acute myocardial ischemia-reperfusion injury, and to detect the role of mitogen activated protein kinase(MAPK) during the injury.METHODS: Rats were randomly divided into five groups: sham group, reperfusion injury(R/I) group, gradually decreased reperfusion group(GDR group, 30/10-25/15-15/25-10/30 seconds of reperfusion/ischemia), equal reperfusion group(ER group, 20/20 seconds reperfusion/ischemia, 4 cycles), and gradually increased reperfusion group(GIR group, 10/30-15/25-25/15-30/10 seconds of reperfusion/ischemia). Acute myocardial infarction and ischemic post-conditioning models were established in the rats. Six hours after reperfusion, 3 rats from each group were sacrificed and myocardial tissues were taken to measure the expressions of phosphorylation of extracellular signalregulated protein kinase(P-ERK), phosphorylated c-Jun N-terminal kinase(P-JNK), mitogen-activated protein kinase p38(p38 MAPK), tumor necrosis factor-α(TNF-α), caspases-8 in the myocardial tissue, and cytochrome c in the cytosol using Western blot. Hemodynamics was measured at 24 hours after reperfusion, the blood was drawn for the determination of cardiac enzymes, and the heart tissue was collected for the measurement of apoptosis using TUNEL. One-way analysis of variance and the Q test were employed to determine differences in individual variables between the 5 groups.RESULTS: Three post-conditioning patterns were found to provide cardioprotection(P<0.05) compared with R/I without postconditioning. GIR provided the best cardioprotection effect, followed by ER and then GDR. Apoptotic index and serum marker levels were reduced more signifi cantly in GIR than in ER(P<0.05). The enhanced cardioprotection provided by GIR was accompanied with significantly increased levels of P-ERK 1/2(1.82±0.22 vs. 1.54±0.32, P<0.05), and lower levels of p-JNK, p38 MAPK, TNF-α, caspase-8, caspase-9 and cytochrome in the cytoplasm(P<0.05), compared with ER. The infarct size was smaller in the GIR group than in the ER group, but this difference was not significant(16.30%±5.22% vs. 20.57%±6.32%, P<0.05). All the measured variables were improved more signifi cantly in the GIR group than in the GDR group(P<0.05).CONCLUSION: Gradually increased reperfusion in post-conditioning could attenuate reperfusion injury more significantly than routine method, thereby the MAPK pathway plays an important role in this process.展开更多
Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern soci- ety. Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads ...Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern soci- ety. Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads to addi- tional damage. Therefore, exploring effective medicines to protect the heart from post-ischemic injury is one of the major objectives of cardiovascular research. Berbamine is a nature compound of bisbenzylisochinoline alkaloids from Barberry. We found that it displays positive inotropic and lusitropic effects at lower concentrations by increasing myofilament Ca2＋ sensitivity via a PKCe-dependent signaling pathway. Moreover, berbamine preconditioning con- fers cardioprotection against ischemia/reperfusion （I/R） injury by attenuating the Ca2＋ overloading and preventing the calpain activation through the activating of PI3K-Akt-GSK3β pathway and subsequently opening of the mitoKATP channel. Furthermore, we demonstrate that berbamine postconditioning conferred the cardioprotective effect against I/R injury by the regulation of autophagy. These findings reveal new roles and mechanisms of berbamine in the heart and cardioprotection against I/R injury.展开更多
文摘Objective: To investigate the protective effect of nitrates postconditioning on myocardial ischemia-reperfusion injury and whether it plays a regulatory role in TNF-α in patients with STEMI during PCI. Methods: Patients with STEMI who underwent PCI were selected, except for obvious anemia, head trauma, cerebral hemorrhage, hypotension (systolic blood pressure less than 90 mmHg), and patients with autoimmune diseases, all kinds of acute and chronic infections and malignant tumors. They were randomly divided into PCI standardized treatment group and isosorbide dinitrate postconditioning during PCI group. The concentrations of cTnI and TNF-α in serum were detected by ELISA method in each group before PCI and after 2 hours, 1 day, 4 days and 7 days of PCI. Results: 1) There were no statistically significant differences in sex, age, smoking history, diabetes, hypertension and blood lipid abnormality in two groups. 2) Before operation, the concentration of cTnI in two groups was not statistically significant. The concentration of cTnI in the experimental group was lower than that of the control group after 4 days and 7 days of PCI, and P α in two groups before operation. The concentration of TNF-α in the experimental group was lower than that in the control group after 1 day, 4 days and 7 days of PCI, and P α in two groups was both in 1 day after operation, and the peak level of the experimental group and the level of each time after the operation were lower than that of the control group. Conclusion: Nitrates postconditioning during PCI in patients with STEMI has a protective effect on myocardial ischemia-reperfusion injury. Nitrates postconditioning has an effect to reduce the level of TNF-α of patients with STEMI after PCI treatment, and may have the mechanism of alleviating the inflammatory response after myocardial ischemia and reperfusion.
文摘BACKGROUND:Ischemia-reperfusion injury occurs when ischemic tissues or organs suffer from further functional and structural damage when their blood supply recovers.This study aimed to contrast the protective effects of ischemic preconditioning and ischemic postconditioning in hepatic ischemia-reperfusion injury in rats.METHODS:Thirty-two healthy male Wistar rats were randomly divided into four groups:sham-operated(SO),ischemia-reperfusion(IR),ischemic preconditioning(I-pre),and ischemic postconditioning(I-post).Blood samples and hepatic tissue were taken from all groups after the experiments.RESULTS:There were significant differences between the IR,I-pre and I-post groups in alanine aminotransferase and aspartate aminotransferase levels,NF-κB p65 expression,apoptosis index and superoxide dismutase activity in hepatic tissue.There were no significant differences between the I-pre and I-post groups.CONCLUSIONS:Ischemic postconditioning and ischemic preconditioning reduce hepatic ischemia-reperfusion injury,but in clinical practice the former is a more appropriate choice.
基金supported by the National Natural Science Foundation of China grant (NSFC81970247)。
文摘Background:Administration of propofol,an intravenous anesthetic with antioxidant property,immediately at the onset of post-ischemic reperfusion(propofol postconditioning,P-PostC) has been shown to confer cardioprotection against ischemia–reperfusion(I/R) injury,while the underlying mechanism remains incompletely understood.The forkhead box O(FoxO) transcription factors are reported to play critical roles in activating cardiomyocyte survival signaling throughout the process of cellular injuries induced by oxidative stress and are also involved in hypoxic postconditioning mediated neuroprotection,however,the role of FoxO in postconditioning mediated protection in the heart and in particular in high glucose condition is unknown.Methods:Rat heart-derived H9c2 cells were exposed to high glucose(HG) for 48 h,then subjected to hypoxia/reoxygenation(H/R,composed of 8 h of hypoxia followed by 12 h of reoxygenation) in the absence or presence of postconditioning with various concentrations of propofol(P-PostC) at the onset of reoxygenation.After having identified the optical concentration of propofol,H9c2 cells were subjected to H/R and P-PostC in the absence or presence of FoxO1 or FoxO3a gene silencing to explore their roles in P-PostC mediated protection against apoptotic and autophagic cell deaths under hyperglycemia.Results:The results showed that HG with or without H/R decreased cell viability,increased lactate dehydrogenase(LDH) leakage and the production of reactive oxygen species(ROS) in H9c2 cells,all of which were significantly reversed by propofol(P-PostC),especially at the concentration of 25 μmol/L(P25)(P<0.05,NC vs.HG;HG vs.HG+HR;HG+HR+P12.5 or HG+HR+P25 or HG+HR+P50 vs.HG+HR).Moreover,we found that propofol(P25) decreased H9c2 cells apoptosis and autophagy that were concomitant with increased FoxO1 and FoxO3a expression(P<0.05,HG+HR+P25 vs.HG+HR).The protective effects of propofol(P25) against H/R injury were reversed by silencing FoxO1 or FoxO3a(P<0.05,HG+HR+P25 vs.HG+HR+P25+siRNA-1 or HG+HR+P25+siRNA-5).Conclusions:It is concluded that propofol postconditioning attenuated H9c2 cardiac cells apoptosis and autophagy induced by H/R injury through upregulating FoxO1 and FoxO3a under hyperglycemia.
基金the National Natural Science Foundation of China,No.31560295(to LYL)the Yunnan Applied Basic Research Projects of China,Nos.2018FE001(-016)(to WM),2018FE001(-163)(to LYL)the Research Innovation Team of Yunnan Province of China,No.2019HC022(to LYL).
文摘During acute reperfusion,the expression profiles of long noncoding RNAs in adult rats with focal cerebral ischemia undergo broad changes.However,whether long noncoding RNAs are involved in neuroprotective effects following focal ischemic stroke in rats remains unclear.In this study,RNA isolation and library preparation was performed for long noncoding RNA sequencing,followed by determining the coding potential of identified long noncoding RNAs and target gene prediction.Differential expression analysis,long noncoding RNA functional enrichment analysis,and co-expression network analysis were performed comparing ischemic rats with and without ischemic postconditioning rats.Rats were subjected to ischemic postconditioning via the brief and repeated occlusion of the middle cerebral artery or femoral artery.Quantitative real-time reverse transcription-polymerase chain reaction was used to detect the expression levels of differentially expressed long noncoding RNAs after ischemic postconditioning in a rat model of ischemic stroke.The results showed that ischemic postconditioning greatly affected the expression profile of long noncoding RNAs and mRNAs in the brains of rats that underwent ischemic stroke.The predicted target genes of some of the identified long noncoding RNAs(cis targets)were related to the cellular response to ischemia and stress,cytokine signal transduction,inflammation,and apoptosis signal transduction pathways.In addition,15 significantly differentially expressed long noncoding RNAs were identified in the brains of rats subjected to ischemic postconditioning.Nine candidate long noncoding RNAs that may be related to ischemic postconditioning were identified by a long noncoding RNA expression profile and long noncoding RNA-mRNA co-expression network analysis.Expression levels were verified by quantitative real-time reverse transcription-polymerase chain reaction.These results suggested that the identified long noncoding RNAs may be involved in the neuroprotective effects associated with ischemic postconditioning following ischemic stroke.The experimental animal procedures were approved by the Animal Experiment Ethics Committee of Kunming Medical University(approval No.KMMU2018018)in January 2018.
基金Supported by Lanzhou City Science and Technology Development Plan,No.2009-1-52
文摘AIM:To investigate the protective effects of remote ischemic postconditioning(RIP)against limb ischemiareperfusion(IR)-induced gastric mucosal injury.METHODS:Gastric IR was established in male Wistar rats by placing an elastic rubber band under a pressure of 290-310 mmHg on the proximal part of both lower limbs for 3 h followed by reperfusion for 0,1,3,6,12or 24 h.RIP was performed using three cycles of 30 s of reperfusion and 30 s of reocclusion of the femoral aortic immediately after IR and before reperfusion for up to 24 h.Rats were randomly assigned to receive IR(n=36),IR followed by RIP(n=36),or sham treatment(n=36).Gastric tissue samples were collected from six animals in each group at each timepoint and processed to determine levels of malondialdehyde(MDA),superoxide dismutase(SOD),xanthine oxidase(XOD)and myeloperoxidase(MPO).Additional samples were processed for histologic analysis by hematoxylin and eosin staining.Blood samples were similarly collected to determine serum levels of lactate dehydrogenase(LDH),creatine kinase(CK),tumor necrosis factor(TNF)-αand interleukin(IL)-10.RESULTS:The pathologic changes in gastric tissue induced by IR were observed by light microscopy.Administration of RIP dramatically reduced the gastric damage score after 6 h of reperfusion(5.85±0.22 vs7.72±0.43;P<0.01).In addition,RIP treatment decreased the serum activities of LDH(3.31±0.32 vs 6.46±0.03;P<0.01),CK(1.94±0.20 vs 4.54±0.19;P<0.01)and the concentration of TNF-α(53.82±0.85vs 88.50±3.08;P<0.01),and elevated the concentration of IL-10(101.46±5.08 vs 99.77±4.32;P<0.01)induced by IR at 6 h.Furthermore,RIP treatment prevented the marked elevation in MDA(3.79±0.29vs 6.39±0.81)content,XOD(7.81±0.75 vs 10.37±2.47)and MPO(0.47±0.05 vs 0.82±0.03)activities,and decrease in SOD(4.95±0.32 vs 3.41±0.38;P<0.01)activity in the gastric tissue as measured at 6 h.CONCLUSION:RIP provides effective functional protection and prevents cell injury to gastric tissue induced by limb IR via anti-inflammatory and antioxidant actions.
文摘This study examined the protective effect of ischemic postconditioning(IPoC) and minocycline postconditioning(MT) on myocardial ischemia-reperfusion(I/R) injury in atherosclerosis(AS) animals and the possible mechanism.Forty male healthy rabbits were injected with bovine serum albumin following feeding on a high fat diet for 6 weeks to establish AS model.AS rabbits were randomly divided into 3 groups:(1) I/R group,the rabbits were subjected to myocardial ischemia for 35 min and then reperfusion for 12 h;(2) IPoC group,the myocardial ischemia lasted for 35 min,and then reperfusion for 20 s and ischemia for 20 s [a total of 3 cycles(R20s/I20s×3)],and then reperfusion was sustained for 12 h;(3) MT group,minocycline was intravenously injected 10 min before reperfusion.The blood lipids,malondialdehyde(MDA),superoxide dismutase(SOD),soluble cell adhesion molecule(sICAM),myeloperoxidase(MPO),and cardiac troponin T(cTnT) were biochemically determined.The myocardial infarction size(IS) and apoptosis index(AI) were measured by pathological examination.The expression of bcl-2 and caspase-3 was detected in the myocardial tissue by using reverse transcription-polymerase chain reaction(RT-PCR).The results showed that the AS models were successfully established.The myocardial IS,the plasma levels of MDA,sICAM,MPO and cTnT,and the enzymatic activity of MPO were significantly decreased,and the plasma SOD activity was significantly increased in IPoC group and MT group as compared with I/R group(P<0.05 for all).The myocardial AI and the caspase-3 mRNA expression were lower and the bcl-2 mRNA expression was higher in IPoC and MT groups than those in I/R group(all P<0.05).It is concluded that the IPoC and MT can effectively reduce the I/R injury in the AS rabbits,and the mechanisms involved anti-oxidation,anti-inflammation,up-regulation of bcl-2 expression and down-regulation of caspase-3 expression.Minocycline can be used as an effective pharmacologic postconditioning drug to protect myocardia from I/R injury.
基金supported by grants from Foundation for Innovative Research Groups of the National Natural Science Foundation of China(81421062)National Natural Science Foundation of China(81470891)+2 种基金863 National High Technology Research and Development Program of China for Young Scientist(2015AA020923)Public Technology Research and Social Development Projects(2016C33145)China Postdoctoral Science Foundation(2017M610374)
文摘Background: Ischemia reperfusion injury(IRI) causes postoperative complications and influences the outcome of the patients undergoing liver surgery and transplantation. Postconditioning(Post C) is a known manual conditioning to decrease the hepatic IRI. Here we aimed to optimize the applicable Post C protocols and investigate the potential protective mechanism.Methods: Thirty Sprague–Dawley rats were randomly divided into 3 groups: the sham group(n = 5),standard orthotopic liver transplantation group(OLT, n = 5), Post C group(OLT followed by clamping and re-opening the portal vein for different time intervals, n = 20). Post C group was then subdivided into 4 groups according to the different time intervals:(10 s × 3, 10 s × 6, 30 s × 3, 60 s × 3, n = 5 in each subgroup). Liver function, histopathology, malondialdehyde(MDA), myeloperoxidase(MPO), expressions of p-Akt and endoplasmic reticulum stress(ERS) related genes were evaluated.Results: Compared to the OLT group, the grafts subjected to Post C algorithm(without significant prolonging the total ischemic time) especially with short stimulus and more cycles(10 s × 6) showed significant alleviation of morphological damage and graft function. Besides, the production of reactive oxidative agents(MDA) and neutrophil infiltration(MPO) were significantly depressed by Post C algorithm. Most of ERS related genes were down-regulated by Post C(10 s × 6), especially ATF4, Casp12, hspa4, ATF6 and ELF2, while p-Akt was up-regulated.Conclusions: Post C algorithm, especially 10 s × 6 algorithm, showed to be effective against rat liver graft IRI. These protective effects may be associated with its antioxidant, inhibition of ERS and activation of p-Akt expression of reperfusion injury salvage kinase pathway.
文摘Objective To investigate the effect of sevoflurane preconditioning and postconditioning on lung ischemia-reperfusion(IR) injury and apoptosis in rat.Methods Wistar rats were randomly assigned to four groups:sham group(n =6):no ischaemia-reperfusion;IR group(n =6):left lung ischemia was achieved by clamping the hilum for 90 min,followed by 120 min reperfusion;sev+pre group(n =6):1 minimum alveolar concentration(MAC) sevoflurane was admi-nistered for 30 min prior to ischemia;sev+post group(n =6):ischemia was followed by 1 MAC sevoflurane postconditioning at the first 30 min reperfusion.PaO2 was measured after reperfusion.The number of apoptotic cells was estimated using the terminal deoxynucleotidyl transferase-mediated dUTP-biotin nick-end labeling(TUNEL) technique.Results After ischemia-reperfusion,a significant deterioration of PaO2 was noticed and the number of apoptotic cells remarkably increased compared with that of sham group.In sev+pre group and sev+post group,PaO2 was(85.7±14.4) mmHg and(88.6±12.5) mmHg respectively,which was apparently increased compared with that in IR group [(63.9±11.3) mmHg,P <0.05].The number of apoptotic cells in sev+pre group [(6.94 ± 1.49)%] and sev+post group [(7.69 ± 1.61)%] was significantly lower than that in IR group [(12.12 ± 2.77)%,P <0.05].But all parameters showed no significant difference between sev+pre group and sev+post group.Conclusions Both sevoflurane preconditioning and postconditioning could prevent lung ischemia-reperfusion injury and attenuate apoptosis in rat.
基金supported by the Joint Fund for Yunnan Provincial Science and Technology Department-Kunming Medical University(No.2017FE467-152)Yunnan Provincial Workstation of XunMing Ji(2018)+2 种基金National Natural Science Foundation of China(Regional Fund Project)(No.81060102)Yunnan Provincial Medical and Health Units set up research institutes for scientific research projects(No.2014NS077,2016NS262,2016NS263,2017NS286,2017NS287)Chinese stroke high-risk population intervention suitable technology research and promotion project(No.GN-2016R0005).
文摘Ischemic postconditioning(IP)has been shown to provide protection for ischemia/reperfusion(IR)injury,but its efficacy is limited.In this study we hypothesized that spontaneous running wheel(RW)could improve neuroprotection efficacy of IP for IR.We established mouse models of IR and showed that compared to Sham group,IR group had obvious brain infract and neurological dysfunction.In IR+IP group,brain infract and neurological dysfunction improved compared to IR group.However,in IR+IP+RW group brain infract and neurological dysfunction improved much better.TUNEL assay showed that IP but not RW significantly reduced the number of apoptotic cells after IR.However,the number of apoptotic cells was significantly reduced in RW+IP group.In addition,the levels of pro-apoptotic factors increased in IR group but significantly reduced in IR+IP+RW group,while the levels of antiapoptotic factors decreased in IR group but significantly increased in IR+IP+RW group.Moreover,in IR+IP+RW group,MDA level was further decreased and SOD level was further increased compared to IR+IP group.Finally,both PI3K inhibitor and STAT3 inhibitor significantly worsened brain infract and neurological dysfunction and promoted apoptosis in IR mice.In conclusion,RW combined with IP reduces brain infract and neurological dysfunction in mice after IR,and this is associated with enhanced anti-apoptotic and anti-oxidant benefits via the activation of PI3K and STAT3 pathways.
基金Shanxi cardiovascular hospital scientific research incentive program(No.XYS20170304)。
文摘Objective:To analyze the influences of locial ischemic postconditioning and remote limb ischemic postconditioning on oxidative stress response with myocardial ischemia reperfusion in rats.Methods:Thirty-two SD rats were randomly divided into Sham group,ischemia/reperfusion(I/R)group,local ischemic postconditioning(LIPC)group,and remote limb ischemic postconditioning(RIPC)group,after 3 hourse reperfusion,the contents of serum creatinine kinase,MB isoenzyme(CK-MB),xanthine oxidase(XOD),superoxide dismutase(SOD),myeloperoxidase(MPO),tumor necrosis factor-α(TNF-α)were measured.The 2,3,5-triphenyltetrazolium chloride(TTC)staining was carried out to evaluate the area of myocardial infarction,cardiac function was evaluated by echocardiography,and HE staining was performed to observe the morphology of myocardial cells.Results:Compared with the Sham group,the SOD contents of the I/R group,LIPC group,RIPC group reduced significantly(P<0.05),the XOD,MPO,TNF-αcontents increased significantly(P<0.05);Compared with the I/R group,the TNF-αcontents of the LIPC group reduced significantly(P<0.05),other oxidative stress indicators of the LIPC group had no significant differences;Compared with the I/R group,the MPO and TNF-αcontents reduced(P<0.05),the SOD and XOD contents of the RIPC group had no significant differences;Compared with the LIPC group,the MPO contents reduced(P<0.05)in the RIPC group,other oxidative stress indicators had no significant differences.Compared with the Sham group,myocardial infarction area,CK-MB contents,LVIDs increased with the reduction of EF in I/R group,LIPC group,RIPC group(P<0.05),HE staining had differences;Compared with the I/R group,myocardial infarction area,CK-MB contents,LVIDd,LVIDs,EF and HE staining results had no significant differences in the LIPC group and the RIPC group;Compared with the RIPC group,the LIPC group had no significant differences.Conclusion:Remote limb ischemic postconditioning and local ischemic postconditioning can partially reduce the oxidative stress response,but does not significantly reduce myocardial infarction area,improve cardiac function.
文摘Objectives To evaluate the effect of hydrogen sulfide(H2S) postconditioning on myocardial ischemia-reperfusion (I/R) by pressure-volume loop(P-V loop). Methods The I/R model of rat in vivo was established by ligating the left anterior descending coronary artery for 30min and reperfusing for 120 min.Wistar rats(n=32) were ran- domly divided into 4 groups;Sham operation,ischemia-reperfusion (I/R),Ischemic postconditioning(IPO) and H2S postconditioning.In sham operation,there was no ligation.In IPO,at the start of reperfusion,three cycles of 30s reperfusion and 30s LAD reocclusion preceded the 3h of reperfusion. In H2S postconditioning,NaHS(15μmol/kg,Sodium hydrosulfide)was administrated before coronary artery reperfusion. The heart rate(HR),I/R arrhythmia,the left ventricular end-systolic pressure(LVESP),left ventricular enddiastolic pressure(LVEDP),the slope of the end- systolic P-V relation(ESPVR) and the slope of the end-diastolic P-V relation(EDPVR) were detected.Infarct size was determined by scanning the images of the rat heart ventricular sections stained with Evans blue and TTC.Results Compared with I/R group,the I/R arrhythmia and the infarct size were decreased significantly(PPP2S postconditioning group.Conclusions Myocardial I/R injury was decreased by H2S post-conditioning, and it was sensitive and accurate to evaluate the heart function by P-V loop.
基金supported by the National Natural Science Foundation of China (No. 30772090)the Natural Science Foundation of Zhejiang Province (Nos. Y204141 and R2090259)+1 种基金the Foundation from Science and Technology Department of Zhejiang Province (No. 2007R10034)the Foundation from the Health Bureau of Zhejiang Province (No. 2007QN007),China
文摘Sevoflurane postconditioning reduces myocardial infarct size.The objective of this study was to examine the role of the phosphatidylinositol-3-kinase(PI3K)/Akt pathway in anesthetic postconditioning and to determine whether PI3K/Akt signaling modulates the expression of pro-and antiapoptotic proteins in sevoflurane postconditioning.Isolated and perfused rat hearts were prepared first,and then randomly assigned to the following groups:Sham-operation(Sham),ischemia/reperfusion(Con),sevoflurane postconditioning(SPC),Sham plus 100 nmol/L wortmannin(Sham+Wort),Con+Wort,SPC+Wort,and Con+dimethylsulphoxide(DMSO).Sevoflurane postconditioning was induced by administration of sevoflurane(2.5%,v/v) for 10 min from the onset of reperfusion.Left ventricular developed pressure(LVDP),left ventricular end-diastolic pressure(LVEDP),maximum increase in rate of LVDP(+dP/dt),maximum decrease in rate of LVDP(?dP/dt),heart rate(HR),and coronary flow(CF) were measured at baseline,R30 min(30 min of reperfusion),R60 min,R90 min,and R120 min.Creatine kinase(CK) and lactate dehydrogenase(LDH) were measured after 5 min and 10 min reperfusion.Infarct size was determined by triphenyltetrazolium chloride staining at the end of reperfusion.Total Akt and phosphorylated Akt(phospho-Akt),Bax,Bcl-2,Bad,and phospho-Bad were determined by Western blot analysis.Analysis of variance(ANOVA) and Student-Newman-Keuls' test were used to investigate the significance of differences between groups.The LVDP,±dP/dt,and CF were higher and LVEDP was lower in the SPC group than in the Con group at all points of reperfusion(P<0.05).The SPC group had significantly reduced CK and LDH release and decreased infarct size compared with the Con group [(22.9±8)% vs.(42.4±9.4)%,respectively;P<0.05].The SPC group also had increased the expression of phospho-Akt,Bcl-2,and phospho-Bad,and decreased the expression of Bax.Wortmannin abolished the cardioprotection of sevoflurane postconditioning.Sevoflurane postconditioning may protect the isolated rat heart.Activation of PI3K and modulation of the expression of pro-and antiapoptotic proteins may play an important role in sevoflurane-induced myocardial protection.
基金Project supported by the National Natural Science Foundation of China (No. 30772090)the Natural Science Foundation of Zhejiang Province (No. Y204141)+1 种基金the Foundation from Science and Tech-nology Department of Zhejiang Province (No. 2007R10034)the Foundation from the Health Bureau of Zhejiang Province (No. 2007QN007), China
文摘Ischemic preconditioning and postconditioning distinctly attenuate ventricular arrhythmia after ischemia without affecting the severity of myocardial stunning. Therefore,we report the effects of sevoflurane preconditioning and postconditioning on stunned myocardium in isolated rat hearts. Isolated rat hearts were underwent 20 min of global ischemia and 40 min of reperfusion. After an equilibration period (20 min),the hearts in the preconditioning group were exposed to sevoflurane for 5 min and next washout for 5 min before ischemia. Hearts in the sevoflurane postconditioning group underwent equilibration and ischemia,followed immediately by sevoflurane exposure for the first 5 min of reperfusion. The control group received no treatment before and after ischemia. Left ventricular pressure,heart rate,coronary flow,electrocardiogram,and tissue histology were measured as variables of ventricular function and cellular injury,respectively. There was no significant difference in the duration of reperfusion ventricular ar-rhythmias between control and sevoflurane preconditioning group (P=0.195). The duration of reperfusion ventricular arrhythmias in the sevoflurane postconditioning group was significantly shorter than that in the other two groups (P<0.05). ±(dP/dt)max in the sevoflurane preconditioning group at 5,10,15,20,and 30 min after reperfusion was sig-nificantly higher than that in the control group (P<0.05),and there were no significant differences at 40 min after reperfusion among the three groups (P>0.05). As expected,for a 20-min general ischemia,infarct size in heart slices determined by 2,3,5-triphenyltetrazolium chloride staining among the groups was not obvious. Sevoflurane postcon-ditioning reduces reperfusion arrhythmias without affecting the severity of myocardial stunning. In contrast,sevoflu-rane preconditioning has no beneficial effects on reperfusion arrhythmias,but it is in favor of improving ventricular function and recovering myocardial stunning. Sevoflurane preconditioning and postconditioning may be useful for correcting the stunned myocardium.
基金Project supported by the National Natural Science Foundation of China (Nos. 81170118 and 81201496)the Zhejiang Provincial Natural Science Foundation of China (No. R2090259)+1 种基金the Medicine Administration Bureau of Zhejiang Province (No. 2011ZZ009)the Department of Science and Technology of Zhejiang Province (Nos. 2009C13G2010218 and 2012C33088),China
文摘It had been proved that administration of sevoflurane for the first two minutes of reperfusion effectively protects the heart against reperfusion injury in rats in vivo.Our aim was to investigate the duration of effective sevoflurane administration and its underlying mechanism in isolated rat hearts exposed to global ischemia/reperfusion(I/R) injury.Adult male Sprague-Dawley rats were randomly divided into six groups(n=12):a sham-operation group,an I/R group,and four sevoflurane postconditioning groups(S2,S5,S10,and S15).In the S2,S5,S10,and S15 groups,the duration times of sevoflurane administration were 2,5,10,and 15 min after the onset of reperfusion,respectively.The isolated rat hearts were mounted on the Langendorff system,and after a period of equilibrium were subjected to 40 min global ischemia and 120 min reperfusion.Left ventricular(LV) hemodynamic parameters were monitored throughout each experiment and the data at 30 min of equilibrium and 30,60,90,and 120 min of reperfusion were analyzed.Myocardial infarct size at the end of reperfusion(n=7 in each group) and the expression of myocardial phosphorylated Akt(p-Akt) after 15-min reperfusion were determined in a duplicate set of six groups of rat hearts(n=5 in each group).Compared with the I/R group,the S5,S10,and S15 groups had significantly improved left ventricular end-diastolic pressure(LVEDP),left ventricular developed pressure(LVDP),and the maximal rate of rise or fall of the LV pressure(±dP/dtmax),and decreased myocardial infarct size(P<0.05),but not the S2 group.After 15 min of reperfusion,the expression of p-Akt was markedly up-regulated in the S5,S10,and S15 groups compared with that in the I/R group(P<0.05),but not in the S2 group.Sevoflurane postconditioning for 5 min was sufficient to activate Akt and exert maximal cardioprotection against I/R injury in isolated rat hearts.
基金supported by a grant from the National Natural Science Foundation of China(810705390)
文摘Background:A rat model for neonatal hypoxic-ischemic brain damage(HIBD)was established to observe the effect of ischemic postconditioning(IPostC)on cerebral edema and the AQP4 expression following HIBD and to verily the neuroprotection of IPostC and the relationship between changes of AQP4 expression and cerebral edema.Methods:Water content was measured with dry-wet method,and AQP4 transcription and the protein expression of the lesions were detected with real-time PCR and immunohistochemistry staining,respectively.Results:Within 6-48 hours,the degree of ipsilateral cerebral edema was significantly lower in IPostC-15 s/15 s group than in HIBD group.Similar to the HIBD group,the AQP4 transcription and expression in the IPostC group showed a downward and then upward trend.But the expression was still more evident in the HIBD group than in the IPostC-15 s/15 s group.From 24 to 48 hours,IPostC-15 s/15 s decreased the slowing down expression of AQP4.Conclusion:IPostC has neuroprotective effect on neonatal rats with HIBD and it may relieve cerebral edema by regulating the expression of AQP4.
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.
基金supported by grants from the National Science Foundation of China(30740080)Dean fund of the General Hospital of Jinan Military Command(2011Q08)
文摘BACKGROUND: Rapid and complete reperfusion has been widely adopted in the treatment of patients with acute myocardial infarction(AMI), but this process sometimes can cause severe reperfusion injury. This study aimed to investigate different patterns of post-conditioning in acute myocardial ischemia-reperfusion injury, and to detect the role of mitogen activated protein kinase(MAPK) during the injury.METHODS: Rats were randomly divided into five groups: sham group, reperfusion injury(R/I) group, gradually decreased reperfusion group(GDR group, 30/10-25/15-15/25-10/30 seconds of reperfusion/ischemia), equal reperfusion group(ER group, 20/20 seconds reperfusion/ischemia, 4 cycles), and gradually increased reperfusion group(GIR group, 10/30-15/25-25/15-30/10 seconds of reperfusion/ischemia). Acute myocardial infarction and ischemic post-conditioning models were established in the rats. Six hours after reperfusion, 3 rats from each group were sacrificed and myocardial tissues were taken to measure the expressions of phosphorylation of extracellular signalregulated protein kinase(P-ERK), phosphorylated c-Jun N-terminal kinase(P-JNK), mitogen-activated protein kinase p38(p38 MAPK), tumor necrosis factor-α(TNF-α), caspases-8 in the myocardial tissue, and cytochrome c in the cytosol using Western blot. Hemodynamics was measured at 24 hours after reperfusion, the blood was drawn for the determination of cardiac enzymes, and the heart tissue was collected for the measurement of apoptosis using TUNEL. One-way analysis of variance and the Q test were employed to determine differences in individual variables between the 5 groups.RESULTS: Three post-conditioning patterns were found to provide cardioprotection(P<0.05) compared with R/I without postconditioning. GIR provided the best cardioprotection effect, followed by ER and then GDR. Apoptotic index and serum marker levels were reduced more signifi cantly in GIR than in ER(P<0.05). The enhanced cardioprotection provided by GIR was accompanied with significantly increased levels of P-ERK 1/2(1.82±0.22 vs. 1.54±0.32, P<0.05), and lower levels of p-JNK, p38 MAPK, TNF-α, caspase-8, caspase-9 and cytochrome in the cytoplasm(P<0.05), compared with ER. The infarct size was smaller in the GIR group than in the ER group, but this difference was not significant(16.30%±5.22% vs. 20.57%±6.32%, P<0.05). All the measured variables were improved more signifi cantly in the GIR group than in the GDR group(P<0.05).CONCLUSION: Gradually increased reperfusion in post-conditioning could attenuate reperfusion injury more significantly than routine method, thereby the MAPK pathway plays an important role in this process.
文摘Myocardial infarction resulting from coronary atherosclerosis is the leading cause of death in modern soci- ety. Reperfusion is an essential treatment to salvage ischemia myocardium from necrosis, while it also leads to addi- tional damage. Therefore, exploring effective medicines to protect the heart from post-ischemic injury is one of the major objectives of cardiovascular research. Berbamine is a nature compound of bisbenzylisochinoline alkaloids from Barberry. We found that it displays positive inotropic and lusitropic effects at lower concentrations by increasing myofilament Ca2＋ sensitivity via a PKCe-dependent signaling pathway. Moreover, berbamine preconditioning con- fers cardioprotection against ischemia/reperfusion （I/R） injury by attenuating the Ca2＋ overloading and preventing the calpain activation through the activating of PI3K-Akt-GSK3β pathway and subsequently opening of the mitoKATP channel. Furthermore, we demonstrate that berbamine postconditioning conferred the cardioprotective effect against I/R injury by the regulation of autophagy. These findings reveal new roles and mechanisms of berbamine in the heart and cardioprotection against I/R injury.
