压力负荷下缬沙坦对钙调神经磷酸酶介导心肌肥大通路的影响

Effects of Valsartan on calcineurin-dependend signal pathway in pressure overload-induced cardiac hypertrophy in rat

目的 :探讨压力超负荷模型下血管紧张素 ( Ang )受体拮抗剂缬沙坦对钙调神经磷酸酶 ( Ca N)介导心肌肥大通路的影响及 Ang 的致心肌肥厚作用。方法 :腹主动脉缩窄法建立大鼠压力超负荷模型 ,放射免疫法检测血浆、心肌 Ang 浓度 ,Western Blot检测心肌 Ca N,活化 T细胞核因子 ( NFAT3 )蛋白表达 ,发色底物法检测 Ca N比活性 ,并测定左室重量指数。结果 :缬沙坦组血浆 Ang 浓度高于对照组 ( P<0 .0 5 ) ,心肌 Ang 浓度则相反 ( P<0 .0 5 ) ,缬沙坦组 Ca N表达及活性低于对照组 ( P<0 .0 1) ,NFAT3 表达低于对照组 ( P<0 .0 5 ) ,两组各项指标与假手术组相比均差异显著。结论 :Ang 参与激活压力负荷下钙调神经磷酸酶通路 。

AIM:To determine the effects of Valsartan on calcineurin dependend signal pathway and evaluate the role of AngⅡ in cardiac pressure overload hypertrophy. METHODS:The model of pressure overload was established by abdominal arota constriction.30 male Wistar rats randomized into three groups,sham operated group,banding group,banding and Valsartan administration group. Two weeks later,Radioimmunoassays measured AngⅡ levels in blood and left ventricular.Western blot measured CaN and NFAT 3 protein content and phosphatase assay measured CaN activity. RESULTS:AngⅡ concentration levels of Valsartan group in myocardia was lower than that of banding group( P <0.05),otherwise in blood( P <0.05).The protein content of CaN and enzyme activity of CaN in banding group were higher than those in Valsartan group significantly( P <0.01),meanwhile,the protein content of NFAT 3 in banding group higher than it in Valsartan group too( P <0.05).The heart/body weight ratio of banding group was higher than Valsartan group. CONCLUSION: AngⅡ involve in promoting the activity of calcineurin dependend signal pathway in pressure overload model.