氯沙坦对肾血管性高血压大鼠心肌细胞肿瘤坏死因子α表达的影响

Effects of Losartan on Expression of TNF-α in Myocardium in Renovascular Hypertensive Rats

目的观察氯沙坦对肾血管性高血压大鼠心肌细胞肿瘤坏死因子α(TNF-α)表达影响。方法实验采用两肾一夹(2K1C)的方法建立肾血管性高血压(RVH)大鼠模型,将大鼠随机分为假手术组、高血压模型组和高血压模型+氯沙坦治疗组(20mg/kg.d);用鼠尾动脉测压法记录每周血压变化,实验末取心脏,并计算心脏指数(CI:心肌重量/体重);ELISA法和免疫组织化学法分别测定各组心肌TNF-α的表达。结果氯沙坦能明显降低肾血管性高血压大鼠的血压(P<0.01)和CI(假手术组:2.86±0.37比高血压模型组:4.12±0.27比氯沙坦组:3.35±0.62,P<0.05)、显著抑制肾血管性高血压大鼠心肌TNF-α的表达[ELISA法:假手术组:1.1±0.1比高血压模型组:31.3±3.0比氯沙坦组:(2.3±0.2)ng/mg,P<0.05]。结论氯沙坦能有效逆转心室重构,其机制可能与降低心肌中TNF-α的表达有关。

Objective To investigate the effect of angiotensin Ⅱ-1 receptor antagonist losartan on expression of tumor necrosis factor-alpha （TNF-α） in the ventricular myocardium in the renovascular hypertension rats. Methods Renovascular hypertension model was obtained by clip left renal artery in Sprague-Dawley（SD） rats. After operation the rats were divided into 3 groups： sham group, two-kidney one clip （2K1C） group, and losartan treatment group（ 2K1C and losartan 20 mg/kg · d by drinking）. Tail blood pressure was determined every week. Animals were euthanized after treatment with losartan for four weeks. Cardiac index（CI）was calculated by HW/ BW, and TNF-α protein of ventricle myocardium was determined by ELISA and immunohistochemistry. Results Losartan significantly decreased blood pressure（ P〈0.01 ）, CI（ sham group： 2.86 ± 0.37 vs 2K1C group： 4.12 ± 0.27 vs losartan group： 3.35 ± 0. 62, P〈0. 05） and the expression of TNF-α in the myocardium （ELISA： sham group：1. 1±0.1 vs 2K1C group：31.3±3.0 vs losartan：2.3±0.2 ng/mg, P〈0. 057. Conclusion Losartan reverse ventricles remodeling in renovascular hypertension rats which was associated with the decreases in TNF-α expression.