盐酸戊乙奎醚对大鼠双下肢缺血再灌注后心肌细胞凋亡的影响

摘要

目的:观察盐酸戊乙奎醚对大鼠双下肢缺血再灌注后心肌细胞凋亡的影响.方法:将实验大鼠随机分为三组:对照组(C组),缺血再灌注(IR)组(H组)和盐酸戊乙奎醚组(M组),每组各20只.观察心组织病理变化,免疫组化法检测心肌组织Bcl-2、Bax和蛋白表达.原位缺口末端标记法(TUNEL法)检测心肌细胞凋亡指数,比色测定心肌超氧化物歧化酶(SOD)活力、组织丙二醛(MDA)、髓过氧化物酶(MPO)含量、夹心法酶联免疫吸附法(ELISA法)测定心肌TNF-α、IL-10含量,统计各组24 h生存率.结果:H组与其他两组比较,心肌组织细胞凋亡指数、心肌组织匀浆MDA、MPO、TNF-α含量、Bax表达明显升高,心肌病变最为严重;H组与C组比较,IL-10含量显著增高;SOD含量、生存率显著下降;M组病变较H组明显改善,生存率明显提高,心肌组织匀浆MDA、MPO、TNF-α含量、Bax表达显著下降;SOD活性、IL-10含量显著增高.结论:肢体缺血再灌注可导致心肌组织局部炎症反应、氧化应激反应增强,引起心脏组织损伤、心肌细胞凋亡;盐酸戊乙奎醚可明显减轻肢体缺血再灌注所引起心肌细胞凋亡,保护心肌,其机制可能是通过减轻心肌局部炎症反应,缓解心肌细胞氧化应激反应实现.%Objective: To investigate effects and mechanisms of Penehyclidine Hydrochloride on apoptosis of myocardial cells induced by ischemia-reperfusion of bi-hind limhs in rats. Methods: Sixty rats were randomly divided into 3 group:sham-operated control (C)group, ischemia-reperfusion (H)group and Penehyclidine Hydrochloride+ischemia-reperfusion (M)group. The cardiac histopatholopic changes in experimental rats were observed . Immunohistochemical studies and TUNEL were done to evaluate the expression of Bax . Bcl-2and the apopt-osis index. Contents of MDA, MPO, IL-10,TNF-α and the activity of SOD in myocardium and the survival rate in 24 hours were measured. Results: In H group: the apoptosis index, the expression of Bax and the contents of MDA, MPO, TNF-α, IL-10 were significantly increased compared with the other two groups. and under light microscope, myocaedial impairment was worst. The activity of SOD and the survival rate of rats significantly decreased compared with C group. In M group: the cardiac histopatholopic changes were hetter than H group, and the survival rate, the contents of IL-10, the activity of SOD significantly increased. The contents of MDA, MPO, TNF-α significantly decreased compared with H group. Condusion: Penehyclidine Hydrochloride can protect the myocardium from bi-limb ischemia-reperfusion, extenuate apoptosis of myocardial cells, and the protective effects may be related to antioxidation and inhibition of inflammatory response.