氯沙坦、福辛普利对SHR心肌细胞凋亡、心肌纤维化及AngⅡ影响(英文)

Effects of Fosinopril versus Losartan on Apoptosis,Myocardial Fibrosis, AngiotensinⅡ in the Left Ventricle of Hypertensive Rats

目的 评价氯沙坦、福辛普利对自发性高血压大鼠 (SHR)心肌细胞凋亡、心肌纤维化及血管紧张素Ⅱ的效应。方法 16周龄SHR随机分为 3组 :氯沙坦治疗组 (SHR L组 )、福辛普利治疗组 (SHR F组 )、空白对照组 (SHR C组 ) ,每组各 10只。分别采用末端脱氧核苷酸转移酶介导dUTP缺口末端标记 (TUNEL)、放射免疫及病理检查方法对治疗 8周、16周心肌细胞凋亡指数 (APOT)、心肌胶原容积分数 (CVF)和心肌血管周围胶原面积 (PVCA)、血浆和组织血管紧张素Ⅱ检测。结果 (1)与对照组比较 ,两SHR治疗组 8周、16周后收缩压均有明显下降 ,两组间比较无显著性差异 ;两治疗组SHR心脏肥厚指标左室重量 (LVW )、左室重量指数 (LVWI)均有显著性改善 ,治疗 16周后SHR F组与较SHR L组LVMI显著性减低 ;(2 )与对照组比较 ,治疗 8周后仅SHR F组心肌细胞凋亡指数 (APOI)显著性下降 ,治疗 16周两治疗组APOI均有显著性下降 ,尤以SHR F组下降明显 ;(3)与对照组比较 ,治疗 8周后SHR L、SHR F两组CVF和PVCA有统计学意义下降。治疗 16周后与对照组比较 ,两治疗组CVF和PVCA均显著性下降 ,其中SHR F组CVF较SHR L组下降显著 ;(4)治疗 8周及 16周后 ,SHR F组心肌组织AngⅡ显著下降 ,SHR L组血浆及心肌组织AngⅡ显著增加。结论 两药物均能有?

Objective This study was designed to investigate effects of AT 1 receptor antagonist (losartan) and ACE inhibitor (fosinopril) on cardiomyocyte apoptosis,myocardial fibrosis,and angiotensin Ⅱ (Ang Ⅱ) in the left ventricle of spontaneously hypertensive rats (SHR). Methods This study was performed in 30 SHRs of 16 week old. The rats were randomized to three groups:SHR L(losartan,30 mg·kg -1 ·d -1 ),SHR F(fosinopril,10 mg·kg -1 ·d -1 ),and SHR C (placebo),each group consisting of 10 rats. 5 rats randomly obtained from each group were killed at 8 weeks and 16 weeks of the study respectively. The cardiomyocyte apoptosis was examined by in situ TDT mediated dUTP nick end labeling (TUNEL). The parameters of myocardial fibrosis such as collagen volume fraction(CVF) and perivascular collagen area(PVCA) were determined by pathological examination with computed processing. Ang Ⅱ concentrations of plasma and myocardium were measured by radioimmunoassay. Results The results showed that: (1) Compared with SHR C at 8 weeks and 16 weeks systolic blood pressure was decreased similarly in the both treatment groups. Left ventricular weight and left ventricular mass indexes were lower significantly in the both treatment groups. The left ventricular mass index at 16 weeks was reduced to a lesser extent in SHR F group than that in SHR L group. (2)Compared with SHR C,the cardiomycyte apoptotic index(APOI) at 8 weeks was reduced significantly only in SHR F group,and at 16 weeks in both treatment groups. The APOI of SHR F group was lower than that of SHR L group at 16 weeks. (3)Compared with SHR C, CVF and PVCA at 8 weeks and 16 weeks were reduced significantly in the SHRs treated with either fosinopril or losartan. However,CVF at the latter endpoint in the SHR F was lower than in the SHR L. (4)Compared with SHR C,plasma and myocardium Ang Ⅱ levels at both endpoints were increased significantly in SHR L. However,plasma Ang Ⅱ levels were not changed,and myocardium Ang Ⅱ levels reduced significantly at 8 weeks and 16 weeks in SHR F group. Conclusion These results indicate that either of losartan and fosinopril effectively inhibits cardiomyocyte apoptosis and myocardial fibrosis, and reverses heart hypertrophy. Fosinopril may be more effective in these cardioprotective effects. The effects of ACEI or AT 1 antagonist on myocardiocyte apoptosis,myocardial fibrosis and left ventricular hypertrophy were related to inhibition of myocardium renin angiotensin system.