氯沙坦、福辛普利、氨氯地平对高血压大鼠心肌细胞凋亡及心肌纤维化影响的对比研究

Effects of Losartan, Fosinopril, Amlodipine on Cardiomyocyte Apoptosis, Myocardial Fibrosis, Cardiac Remolding in Hypertensive Rats

目的：评价氯沙坦、福辛普利、氨氯地平对高血压大鼠（ＳＨＲ）心肌细胞凋亡、心肌纤维化及心脏重构效应。 方法：ＳＨＲ随机分为氯沙坦组、福辛普利组、氨氯地平组和对照组。分别治疗８周、１６周后对心肌细胞凋亡。心肌纤维化有关指标进行检测。 结果：①各治疗组治疗８周、１６周收缩压显著下降，心脏重量指数及左心室重量指数显著降低，福辛普利组治疗１６周较其他两治疗组左心室重量指数指标减低。②治疗８周心肌细胞凋亡指数仅福辛普利组下降，治疗１６周各治疗组均下降，尤以福辛普利组明显。③治疗８周福辛普利、氯沙坦两组心肌胶原容积分数和心肌血管周围胶原面积下降；治疗１６周各治疗组均下降，福辛普利组两指标较氨氯地平组下降显著，但仅前指标较氯沙坦组下降明显。④治疗８周及１６周氯沙坦组血浆及心肌组织血管紧张素Ⅱ（ＡｎｇⅡ）增加。治疗８周福辛普利组心肌组织ＡｎｇⅡ下降，治疗１６周福辛普利、氨氯地平两组组织Ａｎｇ Ⅱ均下降，前组较后组显著。 结论：３种药物均能有效逆转心肌肥厚及抗心肌细胞凋亡及心肌纤维化，以福辛普利作用显著，其作用与拮抗心肌组织Ａｎｇ Ⅱ效应有关。

Objective: To investigate the effects of losartan, fosinopril or amlodipine on apoptosis, fibrosis of spontaneously hypertensive rat (SHR)hearts. Methods: SHRs were treated with losartan (SHR-L), fosinopril (SHR-F)or amlodipine (SHR-A), respectively for 8 and 16 weeks. Cardiomyocyte apoptotsis index (APOI), collagen volume fraction (CVF), perivascular circuferential area (PVCA),plasma and myocardium angiotensin Ⅱ (Ang Ⅱ )concentrations were examined. Results: ①Compared with the controls (untreated)at 8 and 16 weeks, systolic blood pressure was decreased similarly in the three groups. Heart weight and left ventricular mass indexes were lower significantly. The reduction of the left ventricular mass index was lower in SHR-F than in the other two groups at 16 weeks. ②Compared with the controls, APOIs were reduced significantly in SHR-F at 8 weeks and in all the three groups at 16 weeks. APOI of SHR-F was the lowest of the three groups at 16 weeks. ③Compared with the controls, CVF, PVCA were reduced significantly in SHR-F and SHR-L at 8 weeks, and in all the three groups at 16 weeks. CVF and PVCA in SHR-F were lower than in SHR-A, and CVF in SHR-F lower than in SHR-L at 16 weeks. ④Compared with the controls at both periods, plasma and myocardium Ang Ⅱ levels were increased significantly in SHR-L, but myocardium Ang Ⅱ level was only reduced significantly in SHR-F at 8 weeks, and in SHR-F and SHR-A at 16 weeks. Conclusion: All the three drugs can inhibit cardiomyocyte apoptosis, prevent myocardial fibrosis and reverse heart hyper- trophy, and fosinopril is best of the three. The mechanism of their cardioprotective effects was associated with the inhibition of myocardium renin-angiotensin-aldsteron system.