血管紧张素Ⅱ-醛固酮诱导肾性高血压大鼠心肌肥厚发生:钙调神经磷酸酶抑制因子的作用

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目的:探讨一肾一夹肾性高血压大鼠模型中,心肌组织中钙调神经磷酸酶(CaN)抑制因子(calcineurin-inhibi-tor,Cain)表达的变化,以及血浆中相关活性因子的变化。方法:将21只健康雄性Wistar大鼠,随机分为3组(n=7),即假手术组、手术组(通过一肾一夹法复制肾性高血压大鼠)及螺内酯组:以螺内酯20 mg/(kg.d)灌胃;实验14 d后,大鼠称质量后抽血处死,分别计算左心室质量(LVW)、全心质量(HW)以及二者与体质量(BW)的比值。采用放射免疫测定法检测血浆醛固酮(Ald)及血管紧张素Ⅱ(AngⅡ)的含量。以蛋白印迹杂交的方法,测定心肌组织中Cain表达的变化。结果:与假手术组比较,手术组大鼠的LVW/BW及HW/BW比值显著增加(P<0.05)、血浆Ald和AngⅡ的水平、及Cain的表达的显著增加(P<0.01);而与手术组比较,螺内酯组大鼠的LVW/BW比值显著减少(P<0.05)、血浆AngⅡ的水平及Cain的表达均显著减少(P<0.01)。结论:通过一肾一夹手术,诱导机体内源性Ald和AngⅡ增加,导致大鼠心肌肥厚反应的发生。同时,机体内源性Cain表达的增加,以抑制CaN信号通路介导的心肌肥厚反应。螺内酯通过阻断Ald与其受体结合,可以抑制心肌肥厚的发生。 Objective: To investigate the changes of calcineurin-inhibi-tor (Cain) expression in myocardium and the changes of plasma related active factors in a rat model of renal hypertensive renal hypertension . Methods: Twenty-one healthy male Wistar rats were randomly divided into three groups (n = 7): sham operation group, operation group (renal hypertensive rats by one kidney and one clamp method) and spironolactone group 20 mg / (kg · d) were given intragastrically. After 14 days, the rats were sacrificed and the blood was sacrificed. The left ventricular mass (LVW), total heart mass (HW) and their relationship with body weight ratio. The levels of plasma aldosterone (Ald) and angiotensin Ⅱ (Ang Ⅱ) were detected by radioimmunoassay. The changes of Cain expression in myocardial tissue were determined by Western blotting. Results: Compared with the sham operation group, the LVW / BW and HW / BW ratios in the operation group were significantly increased (P <0.05), the levels of plasma Ald and AngⅡ and Cain expression were significantly increased (P <0.01) Compared with the surgery group, the LVW / BW ratio of spironolactone group was significantly decreased (P <0.05), and the plasma AngⅡ level and Cain expression were significantly decreased (P <0.01). Conclusion: One kidney and one clip surgery can induce the increase of endogenous Ald and Ang Ⅱ in the body, leading to cardiac hypertrophy in rats. At the same time, the increase of endogenous Cain expression in the body inhibits the cardiac hypertrophy induced by CaN signaling pathway. Spironolactone can inhibit the occurrence of cardiac hypertrophy by blocking the binding of Ald with its receptor.
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