洛沙坦对肾大部分切除肾功能衰竭大鼠心脏的保护作用

Cardioprotective effect of losartan on subtotal nephrectomy renal failure rats

目的探讨洛沙坦对肾大部分切除肾功能衰竭(肾衰)大鼠心脏的保护作用。方法肾大部切除制备肾衰模型(RF组),治疗组(RF+Los组)洛沙坦剂量为10mg·kg-1·d-1灌胃,对照组(Sham组)用生理盐水灌喂。第12周观察实验动物心脏的有关变化。结果RF组大鼠动脉收缩压显著升高,心肌细胞肥大,心肌间质纤维化,而RF+Los组收缩压得到控制,心肌细胞肥大和心肌间质纤维化程度明显减轻。RF+Los组血管紧张素Ⅱ-1型受体(AT1R)mRNA的表达则较RF组显著下调(P<0.05)。结论洛沙坦通过阻断AT1R抑制肾素-血管紧张素系统(RAS)而具有明显的降压及防治肾大部分切除肾衰大鼠左心室肥厚和心肌间质纤维化的作用。

Objective To investigate the cardioprotective effect of losartan o n subtotal nephrectomy renal failure rats. Methods Renal failure rats were estab lished by subtotal nephrectomy, and then divided into RF group with subtotal nep hrectomy,RF+Los group with additional losartan(10 mg·kg-1·d-1) gavage. Rats underwent sham operation(sham group) with normal saline gavage as control. Hear t changes of experimental rats were observed 12 weeks after operation. Results T he RF group developed hypertension of arterial systolic blood pressure(SBP) and myocardiac myocytes hypertrophy. The levels of collagen type Ⅰ,type Ⅲ,and fi bronectin in endocardium and surrounding intracardial coronary arteries adventit ia of the RF group were significantly increased as compared to those of the sham group. The SBP and the levels of collagen type Ⅰ,Ⅲand fibronectin were marked ly decreased in the RF+Los group as compared to those of the RF group.Expressio n of angiotensin Ⅱsubtype 1 receptor (AT1R) mRNA in the myocardium of the RF+L os group was significantly down regulated as compared to that of RF group. Concl usions Losartan can prevent the cardiac ventricular remodeling with left ventric ular hypertrophy (LVH) and myocardial interstitial fibrosis by the depression of renin-angiotensin system through the down-regulation of myocardiac AT1R mRNA.