二氮嗪后处理联合预处理对心肌缺血再灌注损伤作用的研究

Study on the effect of diazoxide postconditioning combined with diazoxide preconditioning on myocardial ischemia/reperfusion injury

目的探讨二氮嗪后处理联合预处理对离体大鼠心肌缺血再灌注损伤的作用。方法 48只Wistar大鼠,建立离体心脏Langendorff装置灌流模型,随机分为如下6组:①对照组(Con组):左冠状动脉前降支(left anteri-or descending artery,LAD)阻断45 min,复灌120 min。②后处理组(Pos组):LAD开放时主动脉灌注管给予6次10秒开放/10秒阻断。③二氮嗪后处理组(Dpo组):二氮嗪(50μmol/L)于复灌时给予。④二氮嗪预处理组(Dpr组):LAD阻断前给予二氮嗪(50μmol/L)。⑤联合组(Cbm组):LAD阻断前、后分别给予二氮嗪(50μmol/L)。⑥阻滞剂组(Dhb组):LAD阻断前、后分别给予二氮嗪(50μmol/L)和5-羟基葵酸盐(100μmol/L)。结果与Con组、Dhb组比较,Pos组、Dpo组、Dpr组、Cbm组的心肌线粒体Flameng评分、心率-收缩压乘积、左心室内压瞬间最大变化速率及冠脉流出液在复灌后各时间点增高(P<0.05),LDH漏出量减少,SOD含量较高,CK及MDA含量低(P<0.05),Cbm组未表现出叠加效应(P>0.05)。结论二氮嗪后处理联合预处理对离体大鼠心肌缺血再灌注损伤有保护作用,但与二氮嗪药物预处理、后处理比较未表现出明显的叠加保护作用。

Objective： To investigate the effect of diazoxide postconditioning combined with diazoxide preconditioning on myocardial ischemia/reperfusion injury in isolated rat heart.Methods： Isolated working heart models of Wistar rats were set up.Forty-eight wistar rats were divided randomly into 6 groups： the Con group in which the left anterior descending artery（LAD） was ligated for 45 mins and followed by 120 mins perfusion;the Pos group in which 6 cycles of 10-seconds-reperfusion and 10-second-occlusion were carried out on the aortic perfusion tube before the full restoration of blood flow;the Dpo group in which the hearts were reperfused with solution containing diazoxide（50 μmol/L） during the reperfusion;the Dpr group in which solution containing diazoxide（50 μmol/L） was perfused before the ligation of LAD;the Cbm group in which solution containing diazoxide（50 μmol/L） was perfused both before and after the ligation of LAD;the Dhb group in which solution containing diazoxide（50 μmol/L） and 5-hydroxydecanoate（5HD,100 μmol/L） was perfused both before and after the ligation of LAD.Results： Compared with Con group and Dhb group,the Flameng score,the pressure-heart rate production,the maximum change rate of left ventricular pressure rise and fall（±dp/dtmax） and coronary flow increased,LDH leakage decreased and the content of SOD was higher,while the content of CK and the content of MDA were lower in Pos group,Dpo group,Dpr group and Cbm group.No additive effect was shown in Cbm group.Conclusion： Diazoxide postconditioning combined with diazoxide preconditioning has cardioprotective effect on myocardial ischemia/reperfusion injury in isolated rat heart,and it shows no additive effect.