丙泊酚或咪达唑仑对大鼠肝缺血再灌注损伤期细胞凋亡及Bcl-2 Bax蛋白表达的影响

Effects of propofol or midazolam on cell apoptosis and Bcl-2/Bax gene expression induced by hepatic ischemia-reperfusion in rats

目的探讨丙泊酚或咪达唑仑对大鼠肝脏缺血再灌注期细胞凋亡及Bcl-2、Bax蛋白表达的影响及其保护作用。方法成年健康SD大鼠72只,随机分为4组:假手术组(Sham组)、缺血再灌注组(IR组)、丙泊酚组(P组)、咪达唑仑组(M组),每组18只。每组又按再灌注时间(1、3、6h)分为3个时相,每个时相各6只。制作70%肝脏缺血再灌注模型,实验结束后即刻取肝左叶做标本。用免疫组织化学法检测Bcl-2与Bax蛋白表达量,末端转移酶标记技术(TUNEL)检测肝细胞凋亡指数(AI),光镜和电镜下观察肝组织的病理学变化。结果与Sham组比较,各组肝组织Bcl-2、Bax蛋白含量、凋亡指数差异有统计学意义(P<0.05);与IR组比较,P、M组Bcl-2蛋白表达增加、Bax蛋白表达和AI减少(P<0.05);与P组比较,M组Bcl-2蛋白表达减少、Bax蛋白表达和AI增加(P<0.05)。IR、P、M组内各时相以再灌注6h最高。光镜和电镜下P、M组的肝细胞病理学变化轻于IR组。结论丙泊酚、咪达唑仑可以通过调节Bcl-2、Bax蛋白表达,使肝细胞凋亡减轻,从而对大鼠缺血再灌注肝脏有一定的保护作用,且丙泊酚的保护作用大于咪达唑仑。

Objective To investigate the effects of propofol or midazolam on cell apoptosis and apoptosisregulating genes gcl-2/Bax expression induced by hepatic ischemia-reperfusion in rats. Methods Seventy-two SD rats were randomly divided into 4 groups（ n = 18 ） ：sham-operated control group（group Sham）, ischemia-reperfusion group（group IR）, propofol group（group P）and midazolam group（group M）. Each group was divided into 3 time phases at 1 h, 3 h, 6 h after reperfusion. To establish a rat model of hepatic ischemia-reperfusion. The left hepatic lobes were sampled at the end of reperfusion, Bcl-2 and Bax protein expression in liver tissue was assessed by immuno-histochemical method. The apoptosis index（AI）of hepatic cell were measured by TUNEI. method. The histological change of liver were observed using light microscopy and electronic microscopy. Results Bcl-2, Bax protein expression and apoptosis index of hepatic cell were statistically different between group Sham and group IR, P, M（P〈0.05）. Bet-2 protein expression was significantly higher while Bax protein expression and AI significantly lower in group P, M than group IR（P〈0.05）. Bcl-2 protein expression was lower while Bax protein expression and AI higher in group M than group P（P〈0. 05）. The result in three time phases of group IR, P, M reached the peak at 6 h after reperfusion. The pathological lesions were lighter in group P, M than that in group IR under light microscopy and electronic microscopy. Conclusion Propofol and midazolam can relieve the liver cellular apoptosis by regulating Bcl-2 and Bax protein expression. They may protect rat from hepatic ischemia-reperfusion injury. And the protective effect of propofol was greater than that of midazolam.