吗啡对大鼠离体心脏再灌注损伤的保护作用

Protective effect of morphine on myocardial reperfusion injury in isolated rat heart

目的研究吗啡对大鼠离体心脏缺血再灌注损伤的保护作用及其机制。方法32只雄性wistar大鼠随机分为对照组,吗啡组,吗啡+纳络酮组,吗啡+格列本脲组,建立离体工作心脏模型。4℃St.ThomasⅡ停搏液诱导心脏停搏30min,观察缺血再灌注后吗啡对心排血量(CO)、左心室压力微分(±dp/dtmax)、左心室舒张压(LVDP)恢复率及乳酸脱氢酶(LDH)、肌酸激酶同工酶(CK-MB)、心肌超微结构的影响,并观察纳络酮和格列本脲对吗啡作用的影响。结果吗啡组CO、±dp/dtmax、LVDP的恢复率优于其他各组(P<0.05),LDH漏出明显低于其他组(P<0.05),心肌线粒体等超微结构损伤明显减轻;纳络酮和格列本脲可以完全阻断吗啡的心肌保护作用。结论吗啡可以减轻大鼠心肌的缺血再灌注损伤。吗啡是通过心脏局部的阿片受体及心肌细胞三磷腺苷(ATP)敏感性钾通道(KATP通道)介导产生心肌保护作用。

Objective To evaluate morphine mediate protective effect on myocardial reperfusion injury in the isolated rat heart and its mechanism. Methods 32 male wistar rats were randomly divided into 4 groups： Control group, morphine group, morphine ＋ naloxone group and morphine ＋ glibenclamide group. The experimental protocol consisted of 15-rain perfusion of KH buffer containing morphine 0.3μmol/L followed by 30-min St. Thomas Ⅱ hospital cardioplegia arrest, ATP-sensitive K^＋ channel inhibitor, glibenclamide, and opioid receptor inhibitor, naloxone, have been administered to interfere in the effect of morphine on myocardium. The recovery of the left ventricular function, release of myocardial enzymes and ultrastructure of myocardium were assessed before and after ischemia. Results The hearts perfused by morphine before cardioplegia arrest had better recovery of cardiac function and lower release of LDH than others group, with myocardial tissue being of general normal structure. The effects of morphine on myocardial protection were eliminated completely by naloxone or glibenclamide. Conclusion Morphine perfusion before cardioplegia arrest can alleviate myocardial reperfusion injury, which is probably mediated by local opioid receptor and KATP channels in myocytes.