氯沙坦对心力衰竭大鼠心肌细胞凋亡及凋亡相关基因蛋白的影响

Effects of Losartan on myocardial cell apoptosis and apoptosis-related gene protein expression in rats with heart failure

目的:应用氯沙坦治疗慢性心力衰竭(心衰)大鼠,探讨其对心肌细胞凋亡的改变及凋亡蛋白Bax、Bcl-2表达水平的影响。方法:采用鼠腹主动脉缩窄术,复制心衰模型。30只大鼠随机分为心衰组、治疗组和对照组,每组10只。治疗组给予氯沙坦30mg·kg-1·d-1灌胃,心衰组和对照组分别给予同量0.9%氯化钠溶液灌胃;在3个月末测量血流动力学指标后,将大鼠处死,取出心脏,用原位脱氧核糖核酸酶末端标记法检测心肌细胞凋亡情况,免疫组织化学染色法检测心肌Bax与Bcl-2蛋白表达。结果:与对照组比较,心衰组心功能明显减退,心肌细胞凋亡指数明显增加,心肌细胞Bcl-2蛋白表达减少、Bax蛋白表达增加(均P<0.05),Bcl-2/Bax的比率降低;与心衰组比较,治疗组心室重构改善,心肌细胞凋亡减少,Bcl-2表达增加、Bax表达减少(均P<0.05)。结论:心衰大鼠的心肌细胞凋亡增加与Bcl-2蛋白表达降低、Bax蛋白表达增加有关。减少Bax的同时增加Bcl-2蛋白表达水平,可以抑制心肌细胞凋亡,并改善心功能。

Objective：To study the effects of Losartan therapy on the myocardial apoptosis and expression of proapoptotic protein Bax and antiapoptotic protein Bcl-2 in rats with chronic pressure overloard heart failure （CHF）. Method：The rat model of CHF was induced by transverse abdominal aortic constricton. Thirty rats were divided into three groups： CHF group （n= 10）, treatment group （n=10） and control group （n= 10）. Treatment group was administrated with Losartan （30 kg-1 d-1）, while CHF group and control group with 0. 9% Nacl. After three months, these rats were killed after measurement of hemodynamic parameters, then removed hearts and assessed apoptosis with TUNEL method, and determined the expression of proapoptotic Bax, and antiapoptot- ic Bcl-2 genes by immunohistochemistry and image analysis. Result：Compared to control group, there was signifi- cant systolic dysfunction in CHF group, and the myocardial apoptosis was significantly increased, the expression of Bcl-2 was reduced while Bax was increased （all P〈0.05）, the Bcl-2/Bax ratio was reduced too. Compared to CHF group, there was significant improvement of heart function in treatment group, and the myocardial apoptosis was significantly decreased, the expression of Bcl-2 was reduced while Bax was decreased （all P〈0.05）. Conclu- sion：The date suggest that in chronic pressure overload heart failure, increased cardiomyocyte specific apoptosis are related with elevating Bax expression and reducing Bcl-2 expression. Losartan ameliorate systolic dysfunction can reduce myocardial apoptosis and prevent the changes of Bcl-2 and Bax.