阿托伐他汀抑制血管紧张素Ⅱ诱导心房肌细胞肥大及对缝隙连接蛋白40的影响

Effect of atorvastatin on the hypertrophy and Cx40 expression of atrial myocytes induced by angiotensinⅡ

目的观察阿托伐他汀对血管紧张素Ⅱ(AngⅡ)诱导的心房肌细胞肥大及缝隙连接蛋白40(Cx40)表达的影响。方法20只1周龄左右Wistar大鼠,用于体外心房肌细胞的分离培养与鉴定。设置正常对照组、AngⅡ(1μmol/L)组、AngⅡ+二甲亚砜组和AngⅡ+阿托伐他汀0.1、1.0、10μmol/L共6组。72h后利用氚标亮氨酸掺入法检测心房肌细胞蛋白合成速率,逆转录聚合酶链反应分别检测脑钠肽的前体(Nppb)、转化生长因子(TGF)-β_1及Cx40 mRNA的表达。结果与正常对照组相比,AngⅡ组氚标亮氨酸掺入量和Nppb mRNA表达呈显著性增加(P<0.05),同时TGF-β_1 mRNA高表达而Cx40mRNA低表达,阿托伐他汀逆转上述变化,10μmol/L组作用最强(P<0.05),而作为溶剂的二甲亚砜无明显作用。结论阿托伐他汀可能通过抑制Nppb mRNA的高表达来逆转AngⅡ诱导的心房肌细胞肥大,抑制TGF-β_1mRNA的高表达减轻心房纤维化,同时可能通过增强Cx40 mRNA的表达来逆转缝隙连接蛋白的重构,最终减低房颤发生率。

Objective To investigate the effect of atorvastatin on angiotensinⅡ（AngⅡ）-induced atrial myocytes hypertrophy and the expression of connexin 40（Cx40）.Methods 20 Wistar rats aged one week were used for culturing primary atrial myocytes and identification.The cells were divided into six groups：normal control group,AngⅡ（1μmol/L）group,AngⅡ＋ dimethyl sulfoxide group,AngⅡ＋atorvastatin 0.1 group,1.0 group,and 10μmol/L group.After 72 h,the synthetic rate of protein in atrial myocytes was detected by ~3H-leucine incorporation.mRNA expression of natriuretic peptide precursor B（Nppb）was the precursor of brain natriuretic peptide and transforming growth factor（TGF）-β1Cx40 was measured by reverse transcription-polymerase chain reaction.Results Compared with normal control group,~3H-leucine incorporation and mRNA expression of Nppb increased significantly in AngⅡgroup（P0.05）,and mRNA expression of TGF-β1increased while mRNA expression of Cx40 decreased.Atorvastatin could reverse those changes,and the effect of 10μmol/L group was the most obvious（P0.05）,but dimethyl sulfoxide as the solvent had no effects.Conclusion Atorvastatin inhibits hypertrophy of atrial myocytes induced by AngⅡthrough inhibiting the increase of mRNA expression of Nppb,and inhibiting the increase of mRNA expression of TGF-β1to decrease atrial fribosis,while may reverse the remolding of connexin by increase of mRNA expression of Cx40 to reduce the incidence rate of atrial fibrillation in the end.