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目的:探讨吗啡预处理对大鼠缺血再灌注损伤心肌保护作用及对线粒体通透性转换孔(mitochondrial permeability transition pore,MPTP)的影响。方法:40只SD成年雄性大鼠,体质量220～280 g,随机分为S组(假手术组,仅穿线,不结扎冠状动脉前降支),IR组(缺血再灌注组),Mp+IR组(吗啡预处理缺血再灌注组),CsA+IR组(环孢霉素A预处理缺血再灌注组),每组10只。除S组外,其余大鼠心脏都经历30 min缺血和180 min再灌注,再灌注180 min时抽血测血清中磷酸肌酸同工酶(creatine kinase-Mb,CK-Mb)和心肌肌钙蛋白I(cardiac troponin I,cTnI),分离心肌线粒体,测定缺血再灌注心肌线粒体2-3[H]DOG,Cyt C,[Ca2+]m和Ca2+摄取速率及MPTP t1/2(MPTP达到50%开放所需时间)并比较4组之间的差异。结果:Mp+IR组和CsA+IR组CK-Mb与cTnI明显较IR组降低(P<0.01)。IR组心肌细胞线粒体2-3[H]DOG和[Ca2+]m明显增加,高于S组,Cyt C含量明显低于S组,Mp+IR组较IR组2-3[H]DOG和[Ca2+]m下降,Cyt C含量增加(P<0.01)。2-3[H]DOG与[Ca2+]m呈正相关(r=0.797,P<0.01),Cyt C与2-3[H]DOG呈负相关(r=-0.805,P<0.01),Cyt C与[Ca2+]m呈负相关(r=-0.648,P<0.01)。缺血再灌注后MPTP t1/2明显缩短,用吗啡和CsA干预使MPTP t1/2明显延长。结论:用吗啡预处理可以起到保护心肌的作用,其机制可能与降低钙超载,延长MPTPt1/2有关。
Objective: To investigate the protective effects of morphine preconditioning on myocardial ischemia-reperfusion injury and its effect on mitochondrial permeability transition pore (MPTP) in rats. Methods: Forty SD adult male rats weighing 220-280 g were randomly divided into three groups: sham-operated group (sham operation group, only threading, non-ligation of the anterior descending coronary artery), IR group (ischemia-reperfusion group), Mp + IR group (Morphine pretreatment ischemia / reperfusion group), CsA + IR group (cyclosporin A preconditioning ischemia reperfusion group), 10 rats in each group. Except for group S, the other rats’ hearts were subjected to 30 min ischemia and 180 min reperfusion. Blood samples were drawn for determination of creatine kinase-Mb (CK-Mb) and cardiac muscle Myocardial mitochondria were isolated from cardiac troponin I (cTnI) and mitochondrial 2-3 [H] DOG, Cyt C, [Ca2 +] m and Ca2 + uptake and MPTP t1 / 2 % Open time required) and compare the differences between the 4 groups. Results: The levels of CK-Mb and cTnI in Mp + IR group and CsA + IR group were significantly lower than those in IR group (P <0.01). The levels of mitochondrial 2-3 [H] DOG and [Ca2 +] m in IR group were significantly higher than those in S group, while the contents of Cyt C in IR group were significantly lower than those in S group Ca2 +] m decreased and Cyt C content increased (P <0.01). The positive correlations were found between DOG and [Ca2 +] m (r = 0.797, P <0.01), and negative correlation between Cyt C and 2-3 [H] DOG And [Ca2 +] m was negatively correlated (r = -0.648, P <0.01). The MPTP t1 / 2 was significantly shortened after ischemia / reperfusion, and the MPTP t1 / 2 prolonged obviously with the intervention of morphine and CsA. CONCLUSION: Pretreatment with morphine can protect myocardium. The mechanism may be related to the decrease of calcium overload and prolongation of MPTPt1 / 2.