PI3K/Akt-NO信号通路在Ang Ⅳ诱导大鼠心肌肥大中的作用

目的研究PI3K/Akt-NO信号通路在血管紧张素Ⅳ(AngⅣ)诱导大鼠心肌细胞肥大中的作用。方法用乳鼠心肌细胞培养,以细胞表面积和心房利钠因子mRNA表达为心肌肥大指标,观察不同浓度AngⅣ对心肌细胞的作用,并观察PI3K阻断剂LY294002和NO合成酶(NOS)抑制剂L-NAME对AngⅣ作用的影响;利用Real-time PCR和Western blot方法检测mR-NA及蛋白水平的表达;硝酸还原法和ELISA法分别检测NO和内皮型NOS(eNOS)含量。结果 AngⅣ浓度依赖地(0.01、0.1及1nmol/L)诱导心肌细胞肥大;使Akt mRNA和蛋白表达明显降低,eNOS mRNA表达以及细胞培养液中eNOS的含量减少,NO的释放下降(P<0.05);LY294002和L-NAME均使AngⅣ的作用加强(P<0.05)。结论 AngⅣ诱导的心肌肥大作用至少部分地与PI3K/Akt-NO信号通路被抑制有关。

Effect of PI3K/Akt-NO signal pathway on cardiomyocyte hypertrophy induced by angiotensin IV in rats

Objective To study the effect of PI3K/Akt-NO signal transduction pathway on cardiomyocyte hypertrophy induced by angiotensin Ⅳ(Ang Ⅳ).Methods The cardiomyocyte hypertrophy responses were assayed by measuring the cell surface area and atrial natriuretic factor mRNA expression in cultured neonatal rat cardiomyocytes.NO concentration and endothelial NO synthase(eNOS) activity were determined by using the nitrate reduction and ELISA methods,respectively.The mRNA and protein expressions were detected by real-time PCR and western blotting,respectively.In cultured cardiomyocytes,LY294002,a selective PI3K antagonist,and L-NAME,a selective NOS antagonist,were used to investigate the mechanisms of Ang Ⅳ.Results In cultured cardiomyocytes,Ang Ⅳ(0.01,0.1,1 nmol/L) induced cardiomyocyte hypertrophy in a concentration-dependent way.Meanwhile,the expressions of Akt mRNA and protein decreased,and the expression of eNOS mRNA and the concentrations of eNOS and NO reduced(P<0.05).LY294002 and L-NAME enhanced these effects of Ang Ⅳ(P<0.05).Conclusion PI3K/Akt-NO signal transduction pathway involves in cardiomyocyte hypertrophy induced by Ang Ⅳ,at least partly.