辛伐他汀对血管紧张素Ⅱ诱导的乳鼠心肌细胞肥大的保护作用及机制研究

Effects and mechanism of Simvastatin on Angiotensin Ⅱ induced myocardial hypertrophy of neonatal rats

目的探讨辛伐他汀(simvastatin,Sim)对血管紧张素Ⅱ(angiotensinⅡ,AngⅡ)诱导的心肌细胞肥大的保护作用及机制。方法采用原代培养新生SD大鼠心肌细胞,以AngⅡ诱导心肌细胞肥大,观察Sim和环孢素A(cyclosporine A,CsA)对心肌肥厚的影响。应用计算机图像分析系统检测心肌细胞体积;考马斯亮蓝法测心肌细胞总蛋白;Till阳离子测定系统(德国)采用DM 3000软件测定胞内[Ca2+]i瞬间变化;Western blotting法检测心肌细胞中钙调神经磷酸酶(calcineurin,CaN)蛋白的含量。结果与AngⅡ组相比,Sim可以抑制AngⅡ诱导的细胞体积和总蛋白的增加(P<0.05),抑制心肌细胞内钙离子浓度([Ca2+]i)瞬间变化幅度(P<0.05),抑制CaN蛋白表达;Sim组与CsA(CaN抑制剂)组相比差异均无统计学意义。结论 Sim抑制AngⅡ诱导的心肌肥厚可能通过调节Ca2+/CaN通路发挥作用。

[Objective] To observe the protective effects and mechanism of Simvastatin on Angiotensin ]] induced myocardial hypertrophy of neonatal rats. [Methods] Using cultured myocardial cells as a model, the cardiomyocytes volume was measured by computer photograph analysis system. The total protein content was measured by the method of coomassie blue staining. [Ca2＋]i transient was measured by Till image system using Fura 2/AM as fluresenee. The expression of calcineurin （CAN） was determinded by Western blotting. [Results] Compared with Ang Ⅱ group, sim could inhibit the protein content and volumes of cultured hypertrophic my- ocardial cells induced by Ang Ⅱ （P〈0.05）, along with decreases in [Ca2＋]i transient （P〈O.05） and the expres- sion of ealeineurin. There is not statistically significant between Sire group and CsA group. [Conclusion] The effects of Sire inhibit myocardial hypertrophy induced by Ang Ⅱ may be related to Ca2＋/calcineurin sigal pathway.