Mischanism Of AMPK-mediated Effect Of Ghrelin On Cardiomyophathy In Goto Kakisaki Wistar Rats

BackgroundGhrelin,a growth hormone releasing peptide,is the endogenous ligand for the growth hormone secretagogue receptor and has been detected in cardiovascular tissues. Recently,some studies indicated that exogenous ghrelin had some protective effects on cardiovascular system.However,the cardioprotective effect and the mechanism of ghrelin have not been elucidated.Diabetes mellitus frequently produces cardiocyte hypertrophy and collagen deposition,changes referred to as LV remodeling.Recently experimental studies have suggested that the AMP-activated protein kinase(AMPK) participate in the regulation of cardioprotective effect.Some studies have also shown that ghrelin is associated with AMPK.In addition,recent studies show that the AMPK pathway was involved in preventing or suppressing LV remodeling through its effects on glucose transporter type 4 and mammalian TOR(mTOR).In the present experiment,we studied the effect on cardiovascular system and expression of AMPK in the heart of the Goto-Kakizaki(GK) rats injected with ghrelin. The effects of ghrelin on the GLUT4 and mTOR associated with AMPK and LV remodeling were also investigated.MethodsGoto-Kakizaki(GK) rats(8-week-old males) were randomly divided into three groups of 8 rats each:Ghrelin(received ghrelin 200 g/kg sc twice daily);Metformin at 350mg/kg sc;saline controls.Normal male Wistar kyoto rats(n=8) served as normal controls.Four weeks later,the effects of ghrelin on cardiac remodeling were evaluated by echocardiographic,hemodynamic,histopathological,and gene expression analysis (AMPK,GLUT4.......,mTOR protein and mRNA expression).The serum level of ghrelin was examined by ELISA.Results1,Goto-Kakizaki(GK) rats were combined with cardiovascular system diseases.2,Ghrelin has the certain protective effects on cardiovascular system.3,Ghrelin prevented ventricular remodeling,increased AMPK and GLUT4 expression in the myocardium,suppressed mTOR protein and mRNA expression.ConclusionsGhrelin has the certain protective effects on cardiovascular system.Ghrelin inhibits ventricular remodeling induced by diabetes mellitus,and the preventive effects of ghrelin may be mediated by the AMPK-depended pathway.