吗啡对大鼠离体工作心脏延迟性保护作用的实验研究

Experiment Study of Morphine Mediate Effect of Delayed Phase of Myocardial Protection in Isolated Working Rat Heart

目的研究吗啡预处理对大鼠离体工作心脏缺血再灌注的延迟性保护作用,并探讨其机制。方法48只Wistar大鼠随机分为6组,每组8只,即对照组、吗啡组、纳络酮组、格列本脲组、吗啡+纳络酮组和吗啡+格列本脲组。腹腔注射给药24h后,建立离体工作心脏模型,4℃St.Thom asⅡ停搏液诱导心脏停搏30min,复灌45min。观察心脏缺血再灌注前后血流动力学恢复率、心肌酶及心肌超微结构的变化。结果吗啡组的心排出量(CO)恢复率、左室发展压(LVDP)恢复率、左室压力微分(±dp/dtmax)恢复率及乳酸脱氢酶(LDH)漏出量均优于对照组(P<0.05);30min缺血再灌注后心肌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作用,而单独使用纳络酮或格列本脲对大鼠心脏不产生影响。结论吗啡预处理对缺血心肌可以产生延迟性保护作用,其作用与阿片受体和心肌细胞ATP敏感性钾通道(KATP通道)介导有关。

OBJECTIVE To investigate morphine mediate effect of delayed cardioprotection in rat heart. METHODS 48 male wistar rats were randomly divided into 6 groups with 8 animals in each group. There are 0.9% sodium chloride,morphine,naloxone, glibenclamide, morphine ＋ naloxone and morphine ＋ glibenclamide, according to different groups were administered via intraperitoneal injection. 24 hours late, the heart arrested 30 minutes with 4 ℃ St. Thomasllcardioplegic solution infusion following 45 minutes normothermic reperfusion in the isolated working rat heart. The recovery of hemodynamic effects, release of myocardial enzymes and ultrastructure of myocardium were assessed before and after ischemia. RESULTS Morphine pretreatment significantly improved the recovery percentage of postischemic CO,LVDP and ＋dp/dt （ P 〈0.05）. Meanwhile,a lower release of LDH and ultrastructural integrity of myocardium were observed in morphine group after reperfusion. The cardioprotection effects of morphine could be abolished by naloxone or glibenclamide. CONCLUSION Morphine pretreatment can induce a delayed phase of cardioprotection via opioid receptors and KATP channels.