Metformin attenuates pressure overload-induceced cardiac hypertrophy via AMPK activation  

作　　者：Yong-nan FU Han XIAO Xiao-wei MA Sheng-yang JIANG MingXU You-yi ZHANG 

机构地区：[1]Institute of Vascular Medicine, Peking University Third Hospital and Key Laboratory of Molecular Cardiovascular Sciences, Ministry ofEducation, BeiJing 100191, China

出　　处：《Acta Pharmacologica Sinica》2011年第7期879-887,共9页中国药理学报（英文版）

摘　　要：Aim： To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect. Methods： Wild type and AMPKα2 knockout （AMPKα2-/-） littermates were subjected to left ventricular pressure overload caused by transverse aortic constriction. After administration of metformin evaluated using echocardiography and anatomic and histologica lyzed using Western blotting. （200 mg·kg^-l·d^-1） for 6 weeks, the degree of cardiac hypertrophy was methods. The antihypertrophic mechanism of metformin was anaResults： Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKα2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B （AKT） and mammalian target of rapamycin （mTOR） in response to pressure overload in wild type mice, but not in AMPKα2-/- mice. Conclusion： Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.Aim： To identify the role of metformin in cardiac hypertrophy and investigate the possible mechanism underlying this effect. Methods： Wild type and AMPKα2 knockout （AMPKα2-/-） littermates were subjected to left ventricular pressure overload caused by transverse aortic constriction. After administration of metformin evaluated using echocardiography and anatomic and histologica lyzed using Western blotting. （200 mg·kg^-l·d^-1） for 6 weeks, the degree of cardiac hypertrophy was methods. The antihypertrophic mechanism of metformin was anaResults： Metformin significantly attenuated cardiac hypertrophy induced by pressure overload in wild type mice, but the antihypertrophic actions of metformin were ablated in AMPKα2-/- mice. Furthermore, metformin suppressed the phosphorylation of Akt/protein kinase B （AKT） and mammalian target of rapamycin （mTOR） in response to pressure overload in wild type mice, but not in AMPKα2-/- mice. Conclusion： Long-term administration of metformin may attenuate cardiac hypertrophy induced by pressure overload in nondiabetic mice, and this attenuation is highly dependent on AMPK activation. These findings may provide a potential therapy for patients at risk of developing pathological cardiac hypertrophy.

关 键 词：METFORMIN cardiac hypertrophy AMP-activated protein kinase protein synthesis transverse aortic constriction Akt/proteinkinase B mammalian target of rapamycin 

分 类 号：Q463[生物学—生理学] TQ460.6[化学工程—制药化工]