Effects of genistein on cardiac fibrosis of hypertensive mice induced by angiotensin Ⅱ

HUA Xiaofang; SHEN Yanfang

doi:10.3969/j.issn.1002-7386.2016.06.007

Abstract：Objective To investigate the effects of genistein on cardiac fibrosis of hypertensive mice induced by angiotensin Ⅱ(Ang Ⅱ).Methods Thirty male C57BL/6J mice were randomly divided into control group , Ang II group and AngⅡ+genistein group ,with 10 mice in each group .The animal models with cardiac fibrosis were induced by subcutaneous continuous pumping with Ang Ⅱ 1500ng/kg for 7 days, however, the mice in Ang Ⅱ +genistein group were injected subcutaneously with genistein 0 .1μmol/kg on 5 days before pumping Ang Ⅱ, continuously to the end of pumping Ang Ⅱ. The mice in control group were given ethanoic acid instead of pumping Ang Ⅱ.Then the changes of cardiac function of the mice were detected by cardiac echo-cardiography ,the severity of cardiac fibrosis was determined by pathological staining , the expression levels of collagen Ⅰα,collagen Ⅲ,MMP-9,TGF-β1mRNA were measured by Real -time PCR,moreover, the changes of cardiac autophagy were detected by Western Blot for three groups .Results Genistein could obviously improve the cardiac function of mice and relieve the severity of cardiac fibrosis induced by genistein .As compared with those in Ang Ⅱgroup,the LVEF and LVFS in Ang Ⅱ+genistein group were increased ,furthermore, E peak motion velocity during diastole was significantly increased ( P <0.05).The expression levels of collagen Ⅰα, collagen Ⅲ, MMP-9 and TGF-β1 mRNA in AngⅡ+genistein group were significantly decreased , as compared with those in Ang Ⅱgroup ( P <0.05).The results by Western Blot showed that Ang Ⅱ could obviously enhance the expression levels of cardiac autophagy marker -LC3 protein (P<0.05), however, genistein could significantly alleviate the increase of expression levels of LC 3Ⅱcaused by ISO ( P <0.05).Conclusion Genistein can alleviate cardiac fibrosis induced by Ang Ⅱ, and its action mechanism is mainly by improving the cardiac autophagy induced by Ang Ⅱ.