科素亚对心力衰竭大鼠心肌细胞凋亡及Bax、Bcl-2蛋白表达的影响

Effects of cozaar on myocardial apoptosis and expression of Bax and Bcl-2 in rats with chronic heart failure

目的应用科素亚治疗慢性压力负荷性心力衰竭大鼠,探讨其对心肌细胞凋亡及Bax、Bcl-2蛋白表达水平的影响,为心力衰竭发病机制及治疗提供实验依据。方法30只SD大鼠随机分为心衰组(n=10)、治疗组(n=10)和对照组(n=10),采用鼠腹主动脉缩窄术复制心力衰竭模型。治疗组给予科素亚30 mg.kg-1.d-1灌胃,心衰组和对照组分别给予等体积生理盐水灌胃;3个月后测量血流动力学指标,原位脱氧核糖核酸酶末端标记法(TUNEL)检测心肌细胞凋亡,免疫组织化学染色法检测心肌Bax、Bcl-2蛋白表达。结果心衰组与对照组相比,心功能明显减退(P<0.01),心肌细胞凋亡指数明显增加(P<0.01),心肌细胞中Bcl-2蛋白表达减少、Bax蛋白表达增加、Bcl-2/Bax比值降低;治疗组与心衰组相比,心室重构改善(P<0.05),心肌细胞凋亡减少(P<0.01),心肌细胞中Bcl-2表达增加、Bax表达减少(P<0.05)。结论心力衰竭大鼠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蛋白表达,同时增加Bcl-2蛋白表达水平,从而抑制心肌细胞凋亡改善心功能,是科素亚治疗心力衰竭的重要机制之一。

Objective To study the effects of cozaur therapy on myocardial apoptosis and expressions of proapoptotic protein Bax and antiapoptotic protein Bcl - 2 in rats with chronic pressure overload heart failure （ CHF）, and its mechanisms. Methods 30 rats were randomly divided into three groups： CHF group, treatment group and sham operation control group （n = 10 each）. The rat model of CHF was induced by applying transverse abdominal aortic constriction. Treatment was started 6 weeks after the surgery, with cozaur 30 mg/kg p.o.q.d, for the model rats in treatment group, and with NS for the other 2 groups. By the end of 3 months, the hemodynamic parameters were determined, before the rats were killed to remove the heart. The hearts were dissected and weighed, the apoptosis was assessed by using TUNEL method, the expressions of Bax, and Bcl - 2 were determined by immunohistochemistry and image analysis. Results As compared with the control group, the model rats in CHF group showed significant systolic dysfunction （ P 〈 0.01 ）, increased myocardial apoptosis （ P 〈 0.01 ）, and elevated expression of Bax and reduced expression of Bcl - 2. When the results were compared between the treatment and CHF groups, it was found that cozaur treatment resulted in： improved left ventricular remodeling （ P 〈 0.05 ） ; reduced myocardial apoptosis （ P 〈 0.01 ）, and decreased Bax expression and increased Bcl - 2 expression in myocardium （ P 〈 0. 05 ）. Conclusion The data show that in CHF, the increase of mycardial apoptosis is related to the elevation of Bax expression and reduction of Bel - 2 expression, while cozaur can ameliorate the systolic dysfunction and restore the myocardial apeptosis by inverting the above processes.