异丙酚对2型糖尿病大鼠心肌缺血再灌注时细胞凋亡的影响

Effects of propofol on cell apoptosis during myocardial ischemia-reperfusion in rats with type 2 diabetes mellitus

目的探讨异丙酚对2型糖尿病大鼠心肌缺血再灌注时细胞凋亡的影响b方法成年雄性Wistar大鼠，体重160～180g，腹腔注射链脲佐菌素30mg／kg，1次／d，连续2d，制备2型糖尿病模型。取2型糖尿病模型制备成功的大鼠24只，采用随机数字表法，将其分为3组（n=8）：假手术组（S组）、心肌缺血再灌注组（I／R组）和异丙酚组（P组）。采用结扎左冠状动脉前降支30min，再灌注2h的方法制备心肌缺血再灌注损伤模型。P组于缺血前10min开始静脉输注异丙酚6mg·kg＾-1·h＾-1。至再灌注2h。再灌注2h时处死大鼠，取缺血区心肌组织，光镜下观察病理学结果，采用TUNEL法检测心肌细胞凋亡情况，计算凋亡指数（AI）；采用免疫组化法测定Bax和Bcl-2的表达水平；采用Westernblot法检测caspase-3表达水平。结果与S组比较，I／R组和P组心肌组织Bcl-2、Bax和caspase．3的表达上调，AI升高（P〈0．05），心肌发生病理学损伤；与I／R组比较，P组心肌组织Bax和ca$psse-3表达下调，Bcl-2表达上调，AI降低（P〈0．05），心肌病理学损伤减轻。结论异丙酚减轻糖尿病大鼠心肌缺血再灌注损伤的机制与上调Bcl-2表达，下调Bax和caspase-3的表达，抑制细胞凋亡有关。

Objective To investigate the effects of propofol on cell apoptosis during myocardial ischemia- reperfusion （I/R） in rats with type 2 diabetes mellitus （DM）.Methods Adult male Wistar rats, weighing 160-180 g, were used in this study. Type 2 DM was induced by intraperitoneal streptozotocin （STZ） 30 mg/kg once a day for 2 consecutive days. Twenty-four animals with type 2 DM were randomly divided into 3 groups （ n = 8 each） using a random number table： sham operation group （group S）, I/R group and propofol group （group P）. Myocardial I/R was produced by occlusion of the anterior descending branch of left coronary artery for 30 rain followed by 2 h reperfusion. Propofol was infused intravenously at 6 mg·kg^-l ·h^-1 starting from 10 rain before ischemia until 2 h of reperfusion in group P. The animals were sacrificed after 2 h of reperfusion and myocardial specimens in the ischemic region were obtained for microscopic examination and for determination of cell apoptosis and expression of Bax, Bcl-2 and caspase-3. The apoptosis index （AI） was calculated. Results Compared with group S, the expression of Bcl-2, Bax and caspase-3 was significantly up-regulated, and AI was increased, and microscopic examination showed that pathological changes of myocardium were found in I/R and P groups. Compared with group I/R, the expression of Bax and caspase-3 was significantly down-regulated, Bcl-2 expression was up-regulated, AI was decreased, and the pathologic changes were attenuated in group P. Conclusion The mechanism by which propofol attenuates myocardial I/R injury is related to up-regulation of Bcl-2 expression, down-regulation of Bax and caspase-3 expression and inhibition of cell apoptosis in rats with type 2 DM.