阿托伐他汀对大鼠缺血心肌TRAIL表达及细胞凋亡的影响

Study of Atorvastatin on TRAIL expression in myocardiocytes and apoptosis in the rat with acute myocardial infarction

目的:观察阿托伐他汀对大鼠缺血心肌肿瘤坏死因子相关凋亡诱导配体(TRAIL)表达的影响,以及与心肌细胞凋亡和凋亡相关基因Bax、Bcl-2的关系,探讨TRAIL因子在心血管疾病中所起的作用。方法:采用左冠状动脉结扎的方法建立大鼠心肌梗死模型。健康雄性SD大鼠随机分为三组:假手术组、心梗组、阿托伐他汀(10 mg.kg-1.d-1)组。全自动生化分析仪检测血脂水平;病理组织学测定心肌梗死面积;免疫组化及实时定量RT-PCR测定心肌TRAIL、Bax、Bcl-2的表达;TUNEL法测定心肌细胞凋亡。结果:与假手术组相比,心梗组凋亡细胞数显著增加;与心梗组相比,阿托伐他汀组心肌细胞凋亡数显著减少(P<0.01)。与假手术组相比,心梗组Bcl-2/Bax下降;与心梗组相比,阿托伐他汀组Bcl-2/Bax明显上调(P<0.05)。与假手术组相比,心梗组TRAIL在蛋白及基因水平表达明显下降;与心梗组相比,阿托伐他汀组心肌TRAIL蛋白表达显著升高(P<0.01)。结论:阿托伐他汀促使大鼠缺血心肌TRAIL基因表达上调,TRAIL基因可能参与了阿托伐他汀抗心肌细胞的凋亡过程。

Objective： To observe the effect of atorvastatin on TRAIL expression in themyocardiocytes and apoptosis in the rats with acute myocardial infarction （AMI） and the possible role of TRAIL in cardiovascular disease. Methods： The rats with AMI were estab- lished by ligation of the left anterior descending coronary artery. Male Sprague-Dawley rats were randomly divided into three groups： the sham group; the untreated M1 group; the group treated with Atorvastatin 10 mg .kg^-1·d^-1. The level of lipid was analyzed by automatic biochemi-cal analyzer, infarction size was determined by histomorphometric analysis, the expression of TRAIL, Bax and Bcl-2 in the myoeardium was measured with real time RT-PCR and immunohistochemistry, myocardiocytes apoptosis was determined with TUNEL stain. Results： The number of apoptotic cells was significantly increased in the MI group to compare the sham group and atorvastatin markedly inhibited apoptosis in the myocardium after M1 （P〈0.01）, the level of Bcl-2/Bax was down-regulated in the MI group to compare the sham group and signifi- cantly up-regulated in the group treated with Atorvastatin （P〈0.05）, the level of TRAIL protein and gene expression was significantly decreased in the MI group to compare the sham group and markedly increased in the group treated with Atorvastatin （P〈0.01）. Conclusion： Atorvastatin increases the expression of TRAIL in the myocardium in the rats with acute myocardial infarction, the possible role of TRAIL may participate in the anti-apoptosis of atorvastatin in the myocardium.