| Background:Acute myocardial infarction is a serious threat to human health diseases.someresearches revealed, thrombolysis and primary percutaneous coronary interventionsaved the lives of many patients, but also makes coronary recanalization aggravatedmyocardial damage in some patients. Therefore, how to reduce reperfusion aftermyocardial ischemia-reperfusion injury, remains to be explored.Objective:This study was aimed to investigate the effect of pinacidil postconditioning againstmyocardial reperfusion injury in rabbit in vivo and explore its potential mechanism.Methods:1.Experimental groupsThe40healthy adult rabbits were randomly divided into5groups (n=8), shamoperation group (Sham), ischemia reperfusion group (I/R), ischemic postconditioninggroup (I-postC), Pinacidil group (Pina), pinacidil+5hydroxyl decanoate group (Pina+5-HD).2. Model preparationSham Group: silk from the left anterior descending coronary artery (LAD) below thepass through, but not ligation of LAD. I/R group: ligation of LAD30min,followedby120min of reperfusion. I-PostC Group: ligation of LAD30min,at the beginning ofreperfusion, giving three of reperfusion15s/15s as the post-ischemic treatment.Pina Group: at the beginning of reperfusion (in10s), giving pinacidil0.1mg/kgthrough the left ventricular catheter, the other approaches the same way with I/R group. Pina+5-HD groups: at the beginning of reperfusion (in10s), giving pinacidil0.1mg/kg and5-HD5mg/kg through the left ventricular catheter, the otherapproaches the same way with I/R group.3.Outcome measureAfter establishing a successful modeling, Medlab bio-signal acquisition system wasused to continuously monitor the LVSP, LVEDP,±dp/dtmax changes.At the time ofbefore ischemia, ischemia30min, reperfusion for60min,120min reperfusion, CKactivity and MDA content in plasma were detected. After the end of the experiment,the myocardial specimens were sacrificing, Evans blue/triphenyl tetrazolium chloridestaining method was used to determine the area of myocardial ischemia and necrosis,RT-PCR was used to detect the expression of Bcl-2, Bax gene of myocardial cells inischemic area.Result:1.Comparison of Pina group and I/R groupAt the time of reperfusion60min and120min, the level of LVSP and+dp/dtmax inPina group was significantly higher than I/R（P＜0.05）,the level of LVEDP and-dp/dt max,CK activity and MDA content in plasma was lower （P＜0.05）.Moreover,compared with I/R group, the area of myocardial necrosis in Pinagroup was significantly reduced（P＜0.05）, the expression of Bcl-2gene ofmyocardial cells in ischemic area increased（P＜0.05）;the expression of Bax genedecreased significantly（P＜0.05）.2.Comparison of Pina group and Pina+5-HD groupAt the time of reperfusion60min and120min, the level of LVSP and+dp/dtmax inPina group was significantly higher than Pina+5-HD group（P＜0.05）.the level ofLVEDP and-dp/dt max,CK activity and MDA content in plasma was lower（P＜0.05）.In addition,compared with Pina+5-HD group, the area of myocardial infarctionin Pina group was significantly was reduced（P＜0.05）, the expression of Bcl-2gene of myocardial cells in ischemic area increased（P＜0.05）; the expression of Bax genedecreased significantly（P＜0.05）.3.Comparison of Pina group and I-Post groupAt the time of reperfusion60min and120min, all index of cardioc function,CKactivity and MDA content in plasmaan in Pina group had no diifference with I-Postgroup（P＞0.05）,.In addition, there was no fifference in the area of myocardialinfarction and the expression of Bcl-2and Bax gene of myocardial cells in ischemicarea between two group（P＞0.05）.4.Comparison of I-Post group and I/R groupAt the time of reperfusion60min and120min, the level of LVSP and+dp/dtmax inI-Post group was significantly higher than I/R（P＜0.05）, the level of LVEDP and-dp/dt max,CK activity and MDA content in plasma was lower （P＜0.05）.Moreover,compared with I/R group, the area of myocardial infarction in I-Postgroup was remarkably reduced（P＜0.05）, the expression of Bcl-2gene of myocardialcells in ischemic area increased（P＜0.05）;the expression of Bcl-2gene decreased（P＜0.05）.5.Comparison of I-Post group and Pina＋5-HD groupAt the time of reperfusion60min and120min, the level of LVSP and+dp/dtmax inI-Post group was significantly higher Pina＋5-HD（P＜0.05）, the level of LVEDPand-dp/dtmax,CK activity and MDA content in plasma was lower （P＜0.05）,Moreover,compared with Pina＋5-HD group, the area of myocardial infarctionin I-Post group was significantly was reduced（P＜0.05）, the expression of Bcl-2geneof myocardial cells in ischemic area increased（P＜0.05）;the expression of Bax genedecreased significantly（P＜0.05）.6.Comparison of Pina＋5-HD group and I/R groupAt the time of reperfusion60min and120min, all index of cardioc function,CKactivity and MDA content in plasmaan in Pina group had no diifference with I-Postgroup（P＞0.05）,.In addition, there was no fifference in the area of myocardial infarction and the expression of Bcl-2and Bax gene of myocardial cells in ischemicarea between two group（P＞0.05）.Conclusion:1.Both pinacidil postconditioning and ischemic postconditioning can reducemyocardial I/R injury, improving myocardial systolic and diastolic function afterreperfusion, lowering CK activity and MDA content in plasma and reducing the areaof myocardial infarction in ischemic region,hower, pinacidil postconditioning can bemore secure than ischemic postconditioning.2.Mechanism,that pinacidil postconditioning playing against I/R injury, is to openingmitoKATPthrough mimicing the mechanism of ischemic postconditioning3.The function of pinacidil postconditioning playing against I/R injury is related toincreased expression of Bcl-2and decreased Bax gene expression. |
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