吗啡预处理对大鼠缺血再灌注损伤心肌线粒体通透性转换孔的影响(英文)

Effect of morphine preconditioning on mitochondrial permeability transition pore after myocardial ischemia-reperfusion injury in rats

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 effect of morphine preconditioning on mitochondrial permeability transition-pore （MPTP） and its protective mechanism after myocardial ischemia-reperfusion injury. Methods A rat model of ischemia-reperfusion injury was established. Forty rats were injected with 2-3 [ H ] DOG and then divided into 4 groups randomly ： a sham operation （S） group, an ischemiareperfusion injury （IR） group, a morphine preconditioning （Mp ＋ IR） group, and a cyclosporine A pre- conditioning （CsA ＋ IR） group. We monitored the concentrations of serum creatine kinase-Mb （CK-Mb） and cardiac troponin I （cTnI）, and measured myocardial mitochondrial 2-3[ HI DOG, cytochrome c content, Ca2＋ concentration （ [ Ca2＋ ] m）, the velocity of Ca2＋ intake and reaction half time of mitochondrial permeability transition pore （ MPTP t1/2） in the 4 groups. Results The concentrations of serum CK-Mb and cTnI decreased more in the Mp ＋ IR group and the CsA ＋ IR group than those of the IR group. The concentrations of 2-3 [ H ] DOG and [ Ca2 ＋ ] m in the IR group were evidently higher but the level of cyto- chrome c was lower than those of the sham operation group. The concentrations of 2-3 [ H ] DOG and [ Ca2 ＋ ] m in the Mp ＋ IR group decreased whereas the concentration of cytochrome c increased compared with those in the IR group. Mitochondrial 2-3 [ H ] DOG content was positively correlated with the concen- tration of calcium （ r = 0.797, P 〈 0.01 ）. The 2-3 [ H ] DOG and [ Ca2 ＋ ] m content were negatively correlated with cytochrome c in the IR group （r = -0. 805 and r = -0. 648, respectively, P 〈0.01 ）. MPTP t1/2 in the IR group was shortened evidently, and that in the Mp ＋ IR and CsA ＋ IR group was significantly lengthened. Conclusion Morphine preconditioning may have myocardial protective effect through unburdening the calcium overload and lengthening the MPTP t1/2.