雷米普利预适应对大鼠心脏延迟性的保护作用

目的探讨雷米普利预适应对大鼠离体心脏缺血-再灌注损伤的延迟性保护作用及机制。方法离体大鼠心脏采用Langendoff灌流法建立心肌缺血再灌注损伤模型。35只大鼠随机分为5组：（1）对照组；（2）缺血-再灌组（I／R组）；（3）雷米普利预处理组（Ramipril 0．05mg／kg）；（4）雷米普利预处理组（Ramipril 0．1mg／kg）：（5）HOE140＋雷米普利预处理组（HOE1400．1mg／kg＋Ramipril 0．1mg／kg）。每组7只。记录左室内压（LVP）、左室内压最大上升速率（＋dp／dtmax）、左室舒张末压（LVEDP）、心率（HR），定时收集冠脉流出液测量冠脉流量（CF）和肌酸激酶（CK）活性。再灌注结束后采用分光光度法测定心肌组织中丙二醛（MDA）含量。结果（1）与对照组比较，I／R组缺血-再灌注后10、20、30min可显著降低LVP和＋dp／dt max（P〈0.01），升高LVEDP（P〈0．01），降低CF（P〈0．01），缺血-再灌注后10、20min显著降低HR（P〈0．01）；（2）与I／R组比较，Ramipril 0．05mg／kg组缺血-再灌注后20、30min可显著升高LVP（P〈0．01）及增加CF（P〈0．05）；缺血-再灌注后10、20、30min可显著升高＋dp／dtmax（P〈0.01），降低LVEDP（P〈0.01）；（3）与I／R组比较，Ramipril 0．1mg／kg组缺血-再灌注后10、20、30min可显著升高LVP（P〈0．01），升高＋dp／dtmax（P〈0.01），降低LVEDP（P〈0.01）；增加CF（P〈0.05）；（4）与Ramipril 0．1mg／kg组比较，HOE1400．1mg／kg＋Ramipril 0．1mg／kg组缺血-再灌注后10、20、30min可显著降低LVP（P〈0.05）；降低＋dp／dtmax（P〈0．05）；升高LVEDP（P〈0.05）；降低CF（P〈0．05）；（5）I／R组缺血-再灌注后10、20、30minCK与对照组比较，均有显著性差异（P均〈0.01）；Ramipril 0．05mg／kg组及Ramipril 0．1mg／kg组缺血-再灌注后10、20、30minCK与I／R组比较，均有显著性差异（P均〈0.01）；HOE1400．1mg／kg＋Ramipril 0．1mg／kg组缺血-再灌注后10、20、30minCK与Ramipril 0．05mg／kg组及Ramipril 0．1mg／kg组比较，均有显著性差异（P均〈0.01）；（6）实验前24h舌下静脉注射雷米普利0．05mg／kg或0．1mg／kg均可显著降低缺血-再灌注心肌组织中MDA含量。结论雷米普利对缺血再灌注诱导离体大鼠心肌损伤具有延迟性保护作用，其机制可能是与激活缓激肽B2受体，减少缓激肽降解有关。

The Delayed-Protective Effect of Ramipril on Myocardial Injury Induced by Ischemia-Reperfusion in Rats

Objective To observe the delayed protective effects of ramipril on myocardial ischemic-reperfusion injury in isolated rat hearts and explore the possible mechanisms.Methods The isolated rat hearts were chosen to make the model of myocardial ischemic-reperfusion injury by developed Langendorff methods.Thirty-five rats were divided into 5 groups randomly:(1) control group;(2) ischemia-reperfusion group;(3) ramipril treatment groups(0.05 or 0.1 mg/kg);(4) Hoe140(0.1 mg/kg) + ramipiril(0.1 mg/kg) group.Left ventricular pressure(LVP),the first derivative of LVP(+dp/dtmax),left ventricular end-diastolic pressure(LVEDP) and heart rate(HR) were recorded.Coronary flow(CF) and creatine kinase(CK) activity were measured by timed collection of coronary effluent.At the end of the reperfusion,the content of malondialdahyde(MDA) was measured.Results(1) 30 minute of global ischemia and 10,20 or 30 min of reperfusion caused a significant cardiac dysfunction as shown by the reduction of LVP and +dp/dtmax,the elevation of LVEDP,and an increase in the release of CK and MDA during reperfusion;and 20 or 30 min of reperfusion caused a significant decrease in HR.(2) Ramipril(0.05 mg/kg) at 24 h after 30 minute of global ischemia and 20 or 30 min of reperfusion raised significantly LVP,CF and +dp/dtmax,decreased LVEDP.(3) Ramipril(0.1 mg/kg) at 24 h after 30 minute of global ischemia and 10,20 or 30 min of reperfusion raised significantly LVP,CF and +dp/dtmax,decreased LVEDP.(4) The myocardial protection of ramipril was inhibited by HOE140,a bradykinin B2 receptors antagonist.(5) The release of CK in ischemia-reperfusion(30 min ischemia and 10,20 or 30 min reperfusion) group were significant increased compared with control,while ramipril treatment(0.05 or 0.1 mg/kg) significantly inhibited an increase in the release of CK induced by ischemia-reperfusion;pretreatment with HOE140 markedly decreased the effect of ramipril on the release of CK.(6) Pretreatment with ramipril(0.05 or 0.1 mg/kg) 24 h before the experiment caused a significant reduction of the release of MDA compared with ischemia-reperfusion group.Conclusion These results suggest that the delayed cardioprotection afforded by ramipril may be related to inhibition of bradykinin degradation.