| Background Acute myocardial infarction is one of the most criticallycardiovascular disease.Following an acute coronary artery occlusion, timelymyocardial reperfusion using either primary percutaneous coronary intervention (PCI)or thrombolytic therapy remains the most effective treatment strategy. However, thefull benefits of myocardial reperfusion are not realised. With the reconstruction ofblood supply, reperfusion injury can actually aggravate the condition, and will evenincrease the risk of death in patients. Phosphocreatine is a high-energy phosphatecompounds,it plays a dual function of storing and transporting ATP, application ofexogenous creatine phosphate in myocardial ischemia can reduce the release ofcardiac enzymes, reduce myocardial infarct size.Ischaemic postconditioningrepresents an innovative treatment strategy for limiting lethal myocardial reperfusioninjury and further reducing myocardial infarct size. Phosphocreatine and ischemicpostcondjtioning’s mechanism in ischemia-reperfusion injury remain to beconfirmed by further studies.Objectives The purpose of this study was to establish in vivo myocardial ischemiaand reperfusion model, to investigate the combined effect of Phosphocreatine(Pcr)and ischemic postconditioning(IPost)on myocardial ischemia-reperfusion(I/R) injuryin rat model, to observe their impact on myocardial enzymes, myocardial infarct size, to investigate their myocardial protective mechanism.Methods In anesthetized open-chest Sprague-Dawley rats， the left anteriordescending artery(LAD)was occluded for30min and reperfused for120min.All ratswere randomly divided into four groups(n=10in each group)：Sham group，I/R groupwithout other interventions, Ipost group with3cycles of10s reperfusion and10sischemia， PCr+IPost (PCr was applied200mg/kg through the femoral beforereperfusion5min and IPost before reperfusion). Myocardial infarct size (IS) wasmeasured by2,3,5-Triphenyltetrazolium chloride staining at the end of theexperiment, the activity of Serum creatine kinase (CK), Lactate dehydrogenase(LDH)，myeloperoxidase（MPO）were measured after120min of reperfusionrespectively, serum level of tumor necrosis factor-α(TNF-α）and Nuclear factor–κB（NF-κB） were detected by ELISA.Myocardial expression of phosphoryated AKTand BCL-2were determined by western blot.Results1. CK,LDH,MPO were all significantly reduced in IPost group comparedwith the I/R group(P＜0.05),these benefical effects were further enhanced byPCr+IPost group(P＜0.05);CK,LDH,MPO were all significantly increased inPCr+IPost group compared with the sham group(P＜0.05).2.Body Weight and left ventricular weight in each group were not statisticallydifferent(P＞0.05). The ischemic risk area of the PCr+IPost group is less than theIPost group and I/R group(P＜0.05), no significant difference between the other twogroups. IS was significantly reduced in IPost group compared with the I/R group(P＜0.05),these benefical effects were further enhanced by PCr+IPost group(P＜0.05).3.TNF-α,NF-κB were all significantly reduced in IPost group compared with the I/Rgroup(P＜0.05),these benefical effects were further enhanced by PCr+IPost group(P＜0.05); TNF-α,NF-κB were all significantly increased in PCr+IPost group comparedwith the sham group(P＜0.05).4.P-AKT and BCL-2were significantly increased in IPost group compared with theI/R group(P＜0.05), these benefical effects were further enhanced by PCr+IPostgroup(P＜0.05). 5.NF-κB levels were positively correlated with the levels of TNF-α (rs=0.902, P＜0.01).6.TNF-α levels were positively correlated with the levels of MPO(rs=0.663，P＜0.01）.7.P-AKT were positively correlated with the levels of BCL-2（rs=0.921，P＜0.01）.Conclusions1.the results indicate that PCr+IPost could alleviate myocardialischemia-reperfusion injury in rat model by activating PI-3K/AKT/BCL-2signalingpathway and inhibiting TNF-αinflammatory response.2.the results indicate that PCr postconditioning could alleviatemyocardial ischemia-reperfusion injury in rat model by increasing P-AKT/BCL-2signaling pathway and inhibiting inflammatory response. |
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