依达拉奉对大鼠心肌再灌注抗凋亡作用的机制

Anti-apoptosis mechanism of edaravone on myocardial reperfusion in rats

目的:观察大鼠心肌缺血再灌注时依达拉奉抗凋亡作用的机制。方法:采用体外结扎大鼠左前降支制备大鼠心肌缺血再灌注模型。将Wistar大鼠随机分为对照组、缺血再灌注组、依达拉奉组(再灌注即刻经尾静脉注射依达拉奉3mg/kg)。分别用TUNEL染色法及免疫组化法检测心肌细胞凋亡、心肌凋亡蛋白Bcl-2、Bax的表达。结果:(1)凋亡检测结果示,对照组无细胞凋亡,依达拉奉组较缺血再灌注组凋亡细胞数明显减少[(13.11±1.58)比(24.33±1.38),P<0.01];(2)免疫组化结果示,依达拉奉组与缺血再灌注组Bcl-2、Bax蛋白表达均明显高于对照组(P<0.01);依达拉奉组较缺血再灌注组Bcl-2蛋白表达明显升高[(0.2300±0.0218)比(0.0924±0.0152)],而Bax蛋白表达明显降低[(0.0249±0.0042)比(0.1312±0.0173)],P均<0.01;缺血再灌注组Bcl-2/Bax比值较对照组明显降低[(0.6906±0.0035)比(1.1632±0.0212)],依达拉奉组Bcl-2/Bax比值(7.4752±0.5573)较缺血再灌注组和对照组明显升高(P<0.01)。结论:依达拉奉能够减少心肌细胞凋亡,心肌细胞凋亡的减轻与下调Bax蛋白表达,上调Bcl-2蛋白表达以及Bcl-2/Bax比值有关。

Objective： To investigate anti apoptosis mechanism of edaravone on myocardial ischemie reperfusion in rats. Methods： Myocardial isehemic reperfusion model was made by ligated left anterior descending artery in vitro in rats. Wistar rats were randomly divided into control group, ischemie reperfusion group and edaravone group （while reperfusion the rates were immediately injected with edaravone 3mg/kg via tail vein）. Apoptosis of myocardial cells was detected with TUNEL staining method, and expressions of myocardial apoptosis proteins Bcl-2 and Bax were detected with immunohistochemical method. Results： （1） There were no apoptosis in control group, number of apoptotic ceils in edaravone group was significantly less than that of ischemic reperfusion group [（13.11±1.58） vs. （24.33± 1.38）, P〈0.01]; （2） Results of immunohistochemisty indicated that expressions of Bel--2 and Bax proteins in edaravone group and isehemic reperfusion group were significantly higher than that of control group （P〈0.01）; in edaravone group, expression of Bcl-2 protein [（0. 2300±0. 0218） vs. （0. 0924±0. 0152）1 significantly increased and Bax protein [ （0. 0249±0. 0042） vs. （0. 1312±0. 0173）1 significantly decreased compared with those of ischemic reperfusiongroup, P〈0.01 both; ratio of Bcl-2/Bax[ （0.6906±0.0035） vs. （1. 1632±0. 0212）] inischemic reperfusion group significantly decreased compared with control group, Bcl- 2/Bax （7. 4752 ±0. 5573） significantly increased in edaravone group compared with those of isehemie reperfusion group and control group （P〈0.01）. Conclusion： Edaravone can reduce myocardial cells apoptosis. Reduction of myocardial cells apoptosis is related with down regulation of Bax protein expression, upregulation of Bcl-2 protein and Bcl-2/Bax.