缬沙坦降低慢性肾衰竭大鼠心肌内皮素的表达

Valsartan decrease expression of endothelin-1 in myocardium of rats with chronic renal failure

目的:观察缬沙坦对慢性肾衰竭大鼠心肌肥厚及心肌内皮素-1(ET-1)表达的影响,探讨其作用机制。方法:SD雄性大鼠24只,通过5/6肾切除法制备慢性肾衰竭模型,术后2周随机分为模型组、缬沙坦组,并设假手术组作为对照。术后第10周末测定各组大鼠血压及肾功能(BUN、Cr)后处死大鼠,取出心脏进行病理组织形态学观察;并采用原位杂交方法检测心肌ET-1 mRNA转录水平。结果:模型组术后第10周收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数均明显增加,缬沙坦组能显著降低5/6肾切除大鼠收缩压、心脏重量、心脏重量指数、左室重量及左室重量指数(P<0.01);缬沙坦组心肌ET-1 mRNA转录水平较模型组减弱。结论:缬沙坦能改善慢性肾衰竭大鼠的左室肥厚,其机制可能是通过下调心肌ET-1 mRNA转录来实现的。

AIM： To observe the therapeutic effect of valsartan on cardiac hypertrophy and expression of endothelin-1（ET-1） in myocardium of rats with chronic renal failure and explore the mechanism.METHODS： 24 Sprague Dawley male rats were selected,and performed five-sixths nephrectomy to produce chronic renal failure model.Two weeks after the surgery,the rats were randomly divided into model group,valsartan group,and a sham group was established serving as control group.Systolic blood pressure,BUN and serum creatinine were measured at ten weeks after operation,then the rats were sacrificed to take the hearts for pathological histological examination.Hybridization in situ was used to examine the transcription of ET-1 mRNA in myocardium.RESULTS： Systolic pressure,heart weight,heart weight index,left ventricular weight mass（LVM） and left ventricular weight mass index（LVMI） in model group increased significantly tenth week after operation.Systolic pressure,heart weight,heart weight index,LVM and LVMI were decreased markedly in rats with five-sixths nephrectomy by valsartan（P〈0.01）;Hybridization in situ indicated that there was a decreasing expression of ET-1 mRNA in myocardium in valsartan group as compared with model group.CONCLUSION： Valsartan could prevent left ventricular hypertrophy in chronic experiment renal failure rats.The improvement of cardiomyopathy may be through the mechanism of downregulating transcription of ET-1 mRNA in myocardium.