异钩藤碱抑制血管紧张素Ⅱ诱导大鼠心肌细胞肥大的作用

Inhibitory effect of isorhynchophylline on cardiomyocyte hypertrophy induced by angiotensinⅡ

目的研究异钩藤碱(Iso)对血管紧张素Ⅱ(AngⅡ)引起的大鼠心肌肥大的抑制作用,并探讨其机制。方法采用初生大鼠原代心肌细胞培养法,BCA法检测细胞总蛋白含量,测定细胞表面积和心房利钠因子mRNA的表达以观察Iso对AngⅡ诱发心肌细胞肥大的抑制作用。通过测定细胞培养上清液中一氧化氮(NO)含量和一氧化氮合酶(NOS)活性、Real time RT-PCR检测内皮型一氧化氮合酶(eNOS)mRNA的表达,探讨Iso可能的作用机制。结果 AngⅡ0.1μmol·L-1明显促进了心肌细胞肥大,增加心肌细胞表面积、蛋白含量,降低细胞上清液中NO含量及NOS活性,降低eNOS mRNA表达。Iso 1、10μmol·L-1明显抑制AngⅡ诱发心肌细胞肥大的作用,增加细胞中NO的合成、释放和增加NOS活性,上调eNOS mRNA的表达。结论Iso可抑制AngⅡ诱导的心肌细胞肥大,其作用机制可能与促进NOS的活性、增加NO合成和释放有关。

OBJECTIVE To study the inhibitory effect of isorhynchophylline （Iso） on eardiomyoeyte hypertrophy induced by angiotensin Ⅱ （ Ang Ⅱ ） in vitro, and to explore possible mechanisms. METHODS The primary eardiomyocytes were isolated from neonatal rats. The cardiomyocyte surface area, protein content, activity of nitric oxide synthetase （NOS） and content of nitric oxide （NO） were measured. The mRNA expressions of atrial natriuretic factor （ANF） and endothelial nitric oxide synthase （eNOS） of cardiomyocytes were analyzed by Real time RT - PCR. RESULTS 0.10.1 μmol· L-1 Ang Ⅱ significantly induced eardiomyocytes hypertrophy. The cell surface area, protein content and ANF mRNA expression were increased. But the NOS activity and NO content were markedly decreased. 1,10 μmol· L-1 Iso significantly depressed eardiomyocytes hypertrophy by Ang Ⅱ -induced, increased the activity of NOS and release of NO, up - regulated the expression of eNOS mRNA, respectively. CONCLUSION Iso can significantly attenuate the cardiomyocyte hypertrophy induced by Ang Ⅱ , and this effect appears to be related to the increase of NO production and the release.