氯沙坦治疗慢性心力衰竭大鼠心肌细胞凋亡及对促凋亡基因Bax表达的影响  

Effects of losartan on myocardial apoptosis and expression of Bax in rats with chronic heart failure

作　　者：韩斐斐[1] 韩力[2] 王瑾[1] 

机构地区：[1]徐州医学院临床学院诊断学教研室,江苏徐州221004 [2]华中科技大学同济医学院,湖北武汉430030

出　　处：《徐州医学院学报》2012年第11期734-737,共4页Acta Academiae Medicinae Xuzhou

基　　金：徐州医学院课题（09KJ23）

摘　　要：目的应用氯沙坦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的改变及促凋亡蛋白Bmx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。方法选择30只大鼠随机分为心衰组（n=10）、治疗组（n=10）和对照组（n=10）。治疗组给予氯沙坦30mg／（kg·d）灌胃，心衰组和对照组分别给予等量生理盐水灌胃；6周末测量血流动力学指标，将大鼠处死，心肌组织切片分别行免疫组化染色及TUNEL检测。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Bax蛋白表达增加。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），Box在心肌细胞中的蛋白表达减少（P〈0．05）。结论氯沙坦可改善心功能。心力衰竭大鼠的心肌细胞凋亡增加与促凋亡基因Bax表达增加有关。Objective To study the effects of losartan therapy on the myocardial apoptosis and expression of pro- apoptotic protein Bax in rats with chronic pressure overloard heart failure （CHF） , and its mechanisms. Methods 30 rats were divided into three groups： chronic heart failure group, treatment group and control group. Treatment group was administrated with losartan [ 30 mg/（ kg d） , n = 10 ] or no therapy （ CHF, n = 10） or sham operation without constric- tion at all （ control, n = 10） , CHF group and sham group were administrated with normal saline. The CHF rat model was established by transverse abdominal aortic contriction for 6 weeks. After 6 weeks, these rats were killed after measure- ment of hemodynamic parameters and the hearts removed. The left and right ventricles were dissected and weighed sepa- rately. Apoptosis was assessed with TUNEL method. The expression of proapoptotie Bax genes were determined by immu- nohistochemistry and image analysis. Result In CHF rat, there was significant （ P 〈 O. O1 ） systolic dysfunction com- pared to sham. Myocardial apoptosis was significantly increased （ P 〈 0.01 ） , Bax was significantly elevated in chronic heart failure rats, Losartan treatment resulted in： improved left ventricular （LV） remodeling （P 〈0.05 ） ; reduced myo- cardial apoptosis （P 〈 0.01 ） , and selective reduction in myocardial Bax expression （P 〈 0.05 ）. Conclusion The re- suits suggest that in chronic pressure overload heart failure, increased cardiomyocyte specific apoptosis is related with ele- vating Bax expression. Losartan ameliorate systolic dysfunction ean reduee myocardial apoptosis and prevent the changes of Bax.

关 键 词：心力衰竭 细胞凋亡 氯沙坦 Bax 

分 类 号：R446.6[医药卫生—诊断学]