缬沙坦、依那普利、普萘洛尔对未成年自发性高血压大鼠心脏重塑与心肌细胞凋亡的影响

Effect of heart remodeling and cardiac myocyte apoptosis in juvenile spontaneously hypertensive rats un-der the intervention of valsartan.enalapril and propranolol

目的 观察缬沙坦、依那普利、普萘洛尔对未成年自发性高血压大鼠心脏重塑与心肌细胞凋亡的影响及二者的关系,探讨预防性药物干预改善高血压心脏重塑的机制以及心肌细胞凋亡的变化在高血压病早期心脏重塑中的作用和意义。方法 24只4周龄自发性高血压大鼠(SHR),按随机区组设计分为4组,分别应用缬沙坦(30mg·kg-1·d-1)、依那普利(30mg·kg-1·d-1)和普萘洛尔(50mg·kg-1·d-1)干预4周,另设一组为对照组。计算心肌重量指数(CPI)、左心室肥厚指数(LVHI)和右心室肥厚指数(RVHI)。采用末端脱氧核糖核苷酸转移酶介导的带荧光的dUTP缺口末端标记法(TUNEL)对左心室游离壁心肌的凋亡细胞进行检测并进行半定量分析,计算心肌细胞凋亡指数(CMAI)。结果 (1)与对照组比较,依那普利和缬沙坦组CPI和LVHI明显下降(P<0.01),CMAI显著升高(P<0.01)。普萘洛尔组CMAI明显升高(P<0.05),CPI和LVHI呈下降趋势但未达到统计学意义(P>0.05)。(2)未成年SHR LVHI与CPI呈显著正相关(tr-10.856,r=0.918,P<0.001),CPI、LVHI与CMAI呈显著负相关(前者tr=3.917,r=-0.641,P<0.001;后者tr=4.716,r=-0.709,P<0.001)。结论 (1)未成年SHR即存在心肌细胞增生与凋亡的调节失衡,结果导致心脏重量增加,出现心脏重塑。(2)缬沙坦、依那普利。

Objective This study was performed to observe the effect of cardiac myocyte remodeling and apoptosis and their correlation in juvenile spontaneously hypertensive rats under the intervention of valsartan, enalapril and propranolol, to investigate the mechanisms of preventive therapy to improve heart remodeling and the role and meaning of cardiac myocyte apoptosis in earlier stage of hypertension. Methods 24 spontaneously hypertensive rats (SHR) aging 4 weeks were divided into 4 groups according to random blocks design. Treated rats were given one of the following drugs for 4 weeks before they were killed: the AT1 receptor antagonist valsartan(30mg · kg-1 · d-1) ,the angioten-sin-converting enzyme inbibitor enalapril (30mg· kg-1· d-1) the β adrenoceptor blocker propranolol (50mg · kg-1 · d-1). Another group was set up as control. The cardiac ponderal index (CPI), the left ventricular hypertrophy index( LVHI) and the right ventricular hypertrophy index(RVHI) were calculated. Cardiomyocyte apoptosis was assessed in the free wall of left ventricule by in situ TdT-mediated dUTP nick end labeling (TUNEL). Semi-quantitative analysis was used to calculate cardiac myocyte apototic index(CMAI). Results (1)Compared with control group, the CPI and LVHI apparently were lowered,and the CMAI rose notably in enalapril or valsartan group (P<0. 01). In propranolol group the CMAI went up significantly (P<0. 05), the CPI and LVHI tended to descend but showed no statistic significance(P>0. 05). (2)There was a positive correlation between the LVHI and the CPI in juvenile SHR (tr = 10. 856,r=0. 918,P<0. 001). A negative correlation was found between the CPI or the LVHI and CMAI (the former tr = 3. 917,r= -0. 641,P<0. 001; the latter tr=4.716,r=-0. 709,P<0. 001). Conclusion (1)Dysregulation between the cardiac myocyte proliferation and apoptosis occurs even in juvenile SHR, resulting in the increase of heart weight and the heart remodeling. (2)There are different effects on cardiac myocyte remodeling and apoptosis in juvenile SHR under the intervention of valsartan,enalapril and propranolol, indicating distinct mechanisms among these drugs in improving the heatt remodeling. (3)The improvement of genetic heart remodeling in hypertension under antihypertensive drug intervention in earlier period may be ascribed to the upregulation of imbalance between the cardiac myocyte proliferation and apoptosis.