线粒体通透性转换孔在七氟醚延迟预处理减轻大鼠心肌缺血再灌注损伤中的作用

目的 探讨线粒体通透性转换孔(mPTP)在七氟醚延迟预处理减轻大鼠心肌缺血再灌注损伤中的作用.方法 雄性SD大鼠80只,体重250～300 g,随机分为5组(n=16):假手术组(S组)、缺血再灌注组(IR组)、七氟醚延迟预处理组(SP组)、mPTP开放剂苍术苷+七氟醚延迟预处理组(A+SP组)和苍术苷组(A组).IR组、SP组、A+SP组和A组采用结扎左冠状动脉前降支30 min后进行再灌注的方法制备心肌缺血再灌注模型.SP组和A+SP组吸入2.5%七氟醚l h,其余组吸入纯氧1 h,停止吸入后24 h进行心肌缺血.A+SP组和A组在缺血前15 min经尾静脉注射苍术苷5 mg/kg.再灌注120 min时采集颈动脉血样,测定血清肌钙蛋白I(cTnI)浓度.然后处死大鼠,测定心肌梗死体积,检测心肌组织Bcl-2及Bax表达水平,电镜下观察心肌超微结构.结果 与S组比较,其他各组血清cTnI浓度升高,心肌梗死体积扩大,Bcl-2表达下调,Bax表达上调(P＜0.05).与IR组比较,SP组血清cTnI浓度降低,心肌梗死体积缩小,Bcl-2表达上调,Bax表达下调(P＜0.05),心肌病理学损伤减轻.苍术苷可取消七氟醚延迟预处理减轻大鼠心肌缺血再灌注损伤的效应(P＜0.05).结论 抑制mPTP开放后可导致Bcl-2表达上调,Bax表达下调,参与了七氟醚延迟预处理减轻大鼠心肌缺血再灌注损伤.

Role of mitochondrial permeability transition pore in attenuation of myocardial ischemia-reperfusion injury by delayed preconditioning with sevoflurane in rats

Objective To investigate the role of mitochondrial permeability transition pore (mPTP) in attenuation of myocardial ischemia-reperfusion (I/R) injury by delayed preconditioning with sevoflurane in rats.Methods Eighty male SD rats, weighing 250-300 g, were randomly assigned into 5 groups ( n = 16 each): Ⅰsham operation group (group S), Ⅱ group I/R, Ⅲ sevoflurane delayed preconditioning group (group SP), Ⅳ the mPTP opener atractyloside + sevoflurane delayed preconditioning group (group A + SP), and Ⅴ atractyloside group (group A). Myocardial I/R was induced by ligation of anterior descending branch of left coronary artery for 30 min followed by 120 min of reperfusion in group I/R, SP, A + SP and A. In group SP and A + SP, 2.5%sevoflurane was inhaled for 1 h, while pure oxygen was inhaled for 1 h in the other groups, and then myocardial ischemia was performed 24 h later. In group A + SP and A, atractyloside 5 mg/kg was injected intravenously via caudal vein 15 min before ischemia. Blood samples were taken from carotid arteries for detection of serum cardiac troponin-Ⅰ (cTnI) concentrations at the end of reperfusion. Then the rats were sacrificed and hearts removed. The myocardial infarct size (IS) and expression of Bcl-2 and Bax in the myocardium were determined. Myocardial ultrastructure was examined with the electron microscope. Results Serum cTnI concentrations and Bax expression were significantly higher, the myocardial IS was significantly larger and Bcl-2 expression was significantly lower in the other groups than in group S ( P ＜ 0.05). Serum cTnI concentrations and Bax expression were significantly lower, the myocardial IS was significantly smaller and Bcl-2 expression was significantly higher in group SP than in group I/R ( P ＜ 0.05). Microscopic examination showed less damage in group SP than in group I/R. The protection provided by sevoflurane preconditioning was abolished by atractyloside. Conclusion Inhibition of mPTP opening can result in an up-regulation of Bcl-2 expression and down-regulation of Bax expression, which plays a role in attenuation of myocardial I/R injury by delayed preconditioning with sevoflurane in rats.