心阳片通过抑制心肌细胞自噬改善心力衰竭小鼠心功能的作用研究

目的探讨心阳片调节心肌细胞自噬改善心力衰竭(Heart failure,HF)小鼠心功能的作用机制。方法将48只雄性C57BL/6J小鼠随机分为假手术组,模型组,心阳片低、中、高剂量组(455、910、1820 mg·kg^-1)及3-甲基腺嘌呤组(15 mg·kg^-1,腹腔注射给药),每组8只;采用主动脉弓缩窄术复制HF小鼠模型;按上述剂量灌胃给药,灌胃体积为8 mL·kg^-1,每天给药1次,连续4周。采用心脏彩超检测各组小鼠心功能:小鼠左心室射血分数(LVEF)及左室短轴缩短率(LVFS);采用q PCR法检测小鼠心脏组织HF生物标记物B型钠尿肽(BNP)mRNA的表达;采用Western Blot法检测小鼠心肌细胞自噬相关蛋白Beclin-1及LC3BⅡ/Ⅰ的表达。结果与假手术组比较,模型组小鼠的LVEF、LVFS显著降低(P<0.05),BNP mRNA及Beclin-1、LC3BⅡ/Ⅰ蛋白表达明显上调(P<0.05)。与模型组比较,心阳片低、中、高剂量组及3-甲基腺嘌呤组小鼠的LVEF、LVFS显著升高(P<0.05),BNP mRNA及Beclin-1、LC3BⅡ/Ⅰ蛋白表达明显下调(P<0.05)。结论心阳片可能通过抑制心肌细胞过度自噬改善HF小鼠的心功能。

Effect of Xinyang Tablet on Improving Cardiac Function in Mice with Heart Failure by Inhibiting Autophagy of Cardiomyocytes

Objective To investigate the mechanism of Xinyang tablet in regulating cardiomyocytes autophagy for improving cardiac function in heart failure(HF)mice.Methods Forty-eight male C57 BL/6 J mice were randomly divided into Sham operation group,model group,low-dose Xinyang tablet group,medium-dose Xinyang tablet group,high-dose Xinyang tablet group(455,910,1820 mg·kg^-1)and 3-methyladenine group(15 mg·kg^-1).Heart failure model in mouse was induced by transverse aortic constriction(TAC).Mice were given continuous intragastric administration of correspondent drugs and dosages once a day for 4 weeks and the volume of gastric administration was 8 mL·kg^-1.Doppler echocardiography was used to detect the cardiac function of mice.RNA level of gene encoding brain natriuretic peptide(BNP),a biomarker of heart failure,was determined by qPCR.Autophagyrelated proteins were detected by Western Blot.Results Compared with the Sham operation group,the left ventricular ejection fraction(LVEF)and left ventricular shortening fraction(LVFS)were decreased significantly(P<0.05),RNA expression of BNP and the expression of autophagy related proteins(Beclin-1 and LC3 BⅡ/Ⅰ)were significantly increased in model group mice(P<0.05).Compared with the model group,LVEF and LVFS were significantly increased in all dosage groups of Xinyang tablet and 3-methyladenine group(P<0.05),and the levels of BNP,Beclin-1 and LC3 BⅡ/Ⅰwere significantly decreased in these groups(P<0.05).Conclusion Xinyang tablet may improve cardiac function in mice with heart failure by inhibiting excessive autophagy of cardiomyocytes.