Effect of preconditioning with penehyclidine hydrochloride on mitochondria-dependent pathway of apoptosis during myocardial ischemia-reperfusion in rats / 中华麻醉学杂志

ABSTRACT

Objective To evaluate the effect of preconditioning with penehyclidine hydrochloride (PHC)on mitochondria-dependent pathway of apoptosis during myocardial ischemia-reperfusion(I∕R)in rats. Methods Twenty-four healthy adult male Wistar rats were allocated into 3 groups(n=8 each)using a random number table sham operation group(group S), I∕R group and PHC preconditioning group (group P). Myocardial I∕R was produced by occlusion of left anterior descending branch of coronary artery for 30 min followed by 3 h reperfusion. PHC 10 mg∕kg was injected via the tail vein at 30 min before oc-clusion in group P. The rats were sacrificed at the end of reperfusion, hearts were removed and left ventric-ular specimens were obtained for determination of apoptosis in cardiomyocytes(by TUNEL), and apoptosis index(AI)was calculated. Mitochondria and cytoplasm were isolated for detection of mitochondrial mem-brane potential(MMP, by JC-1 method)and expression of Bcl-2, cytochrome c(Cyt c)in mitochondri-a and cytoplasm and activated caspase-3 in myocardial tissues(by Western blot). Results Compared with group S, AI was significantly increased, the expression of Bcl-2 and mitochondrial Cyt c was down-regula-ted, MMP was decreased, and the expression of Cyt c in cytoplasm and activated caspase-3 was up-regula-ted in I∕R and P groups(P<0. 05). Compared with group I∕R, AI was significantly decreased, the ex-pression of Bcl-2 and mitochondrial Cyt c was up-regulated, MMP was increased, and the expression of Cyt c in cytoplasm and activated caspase-3 was down-regulated in group P(P<0. 05). Conclusion The mechanism by which PHC preconditioning attenuates myocardial I∕R injury is related to inhibiting mitochon-dria-dependent pathway of apoptosis in rats.