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Protective effects of the joint application ofremote ischemic preconditioning and sevoflurane postconditioningon myocardial ischemia-reperfusion injury in ratsPurposeEstablish the model of myocardial ischemia-reperfusion injury in rats,to observe the hemodynamic changes,heart systolic and diastolic function changes,serum myocardial biology markers and myocardial infarct size and other indicators of the model during the period of ischemia and reperfusion;to explore the synergistic protective effects of remote ischemic preconditioning and sevoflurane postconditioningon myocardial ischemia-reperfusion injury.MethodsEstablish acute myocardial ischemia-reperfusion injury model on 50 adult SD rats(ischemia 30 min and reperfusion 2h).Then,they were randomly divided into blank control group(CON group),ischemia-reperfusion group(I/R group),remote ischemic preconditioning group(RIPC group),sevoflurane post-treatment group(SPC group)and combined remote ischemic preconditioningand sevoflurane postconditioning group(RIPC+ SPC group).Mmonitor hemodynamics changes(HR,MAP and RPP),arrhythmia and heart function index(LVSP,LVDEP,+dp/dtmax,-dp/dtmax)by Powerlab(a data acquisition and analysis system).Cardiac biology(hs-cTnT,cTnT,CK-MB)and serum concentration were measured by enzyme-linked immunosorbent assay(ELISA).The extent of myocardial infarction was measured by triphenyl tetrazolium(TTC)stainingmethod.ResultsCompared with I/R group,the hemodynamics(HR,MAP and RPP)of RIPC group,SPC group and RIPC + SPC group were more stable,the incidence and severity of arrhythmia were significantly decreased,the cardiac systolic and diastolic function were significantly enhanced,the serum Hs-cTnT,cTnT and CK-MB concentration were significantly reduced,myocardial infarction area was significantly reduced,all the differences were statistically significant.Compared with the RIPC group or the SPC group,the hemodynamics(HR,MAP and RPP)of the RIPC + SPC group were further stabilized,the incidence and score of arrhythmia were further decreased,the cardiac systolic and diastolic function were further enhanced,the serum hs-cTnT,cTnT and CK-MB concentration were further reduced,myocardial infarct size was further reduced,all the differences were statistically significant.ConclusionAdopting the model of myocardial ischemia-reperfusion injury in rats and combining remote ischemic preconditioning with sevoflurane postconditioning,synergistic myocardial protection was achieved and hemodynamic was stabilityand arrhythmia obviously decreasedand cardiac function was improved significantly.Part ? Mechanism research on the joint application ofremote ischemic preconditioning and sevoflurane postconditioningon myocardial ischemia-reperfusion injury in ratsPurposeEstablish the model of myocardial ischemia-reperfusion injury in rats,to explore the mechanism of the inflammatory signaling pathway and the apoptotic pathway involved in protecting myocardium by joint application of remote ischemic preconditioning and sevoflurane postconditioning.MethodsEstablish acute myocardial ischemia-reperfusion injury model on 50 adult SD rats.They were randomly divided into blank control group(Sham group),ischemia-reperfusion group(I/R group),remote ischemic preconditioning group(RIPC group),sevoflurane postconditioning group(SPC group),combined remote ischemia pretreatment with sevoflurane postconditioning group(RIPC + SPOC group).The pathological changes of myocardium were detected by H&E staining method;the levels of serum inflammatory cytokines(IL-8,IL-6 and TNF-?)were measured by ELISA;the TLR4/MyD88/NF-?B(p65)inflammatory pathway was detected by qRT-PCR;Cardiomyocyte Apoptosis Bcl-2/Caspase-3/PARP was detected by TUNEL Method.ResultsCompared with I/R group,in RIPC group,SPC group and RIPC + SPC group,the inflammatory response of cardiomyocytes was significantly reduced;the expression of inflammatory cytokines(including IL-6,IL-8 and TNF-?)was significantly decreased;the expression of mRNA in inflammatory mediators(MyD88,NF-?B(p65))was significantly down-regulated,while anti-inflammatory factor IKB-? expression was up-regulated.Inhibition/proapoptotic gene(Bcl-2/Bax)ratio was significantly increased,the expression of C-Caspase-3 protein was significantly decreased and the expression of PARP protein was significantly increased.Compared with RIPC group or SPC group,the inflammatory response of cardiomyocytes in RIPC + SPC group was further reduced;the expression of inflammatory cytokines(including IL-6,IL-8 and TNF-?)decreased further;mRNA expression of inflammatory mediators(MyD88,NF-?B(P65)was further downregulated,while the anti-inflammatory factor IKB-a expression was further up-regulated.Inhibition/proapoptotic gene(Be 1-2/Bax)ratio was increased further,the expression of C-Caspase-3 protein was further decreased and the expression of PARP protein was further increased.Conclusion1.Combined remote ischemic preconditioningwith sevoflurane postconditioning,the cardiomyocyte inflammatory response and apoptosis were inhibited significantly,myocardial inflammation and apoptosis were reduced and myocardial tissue structure and cell morphology was improved significantly.2.The joint application of remote ischemic preconditioning and sevoflurane postconditioning alleviate the inflammatory response of cardiomyocytes by TLR4/MyD88/NF-?B(p65)inflammatory signal transduction pathway,and reduce the apoptosis of myocardial cell by Bcl-2/Caspase-3/PARP apoptosis signal transduction pathway,and jointly alleviate myocardial ischemia and reperfusion injury,thereby protecting the myocardium. |
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