Ghrelin早期干预改善急性心肌梗死后心肌重构和心脏功能

Early Ghrelin treatment of acute myocardial infarction improves myocardial remodeling and cardiac function

目的探讨急性心肌梗死(myocardial infarction,MI)后Ghrelin早期干预对心脏功能的影响及其机制。方法结扎大鼠冠状动脉左前降支建立急性MI模型,并于1周时Ghrelin干预(100 g·kg^-1皮下注射,每日2次,持续4周)。5周时超声测定心脏功能并直接记录颈交感神经放电。组织病理评估心肌细胞直径、心肌纤维化和梗死面积,Western blot评估心肌心房钠肽(ANP)、脑钠肽(BNP)、β肾上腺素受体(β-adrenergic receptor,β-AR)蛋白表达。结果与假手术相比,MI后5周大鼠心交感神经放电活性明显增强,且左心室功能降低(P<0.01)。Ghrelin可明显抑制MI后心衰大鼠交感神经活性、心肌细胞肥大和心脏纤维化、降低心肌ANP和BNP表达、恢复β-AR表达、改善MI心衰动物的心脏功能。结论本研究表明,Ghrelin早期干预可以减轻MI心肌重塑并预防心力衰竭,其作用机制可能与其抑制交感神经活性和毒性有关。因此,Ghrelin早期干预可能成为心力衰竭治疗的新方法。

Aim To investigate the effects of early Ghrelin treatment on cardiac function after acute myocardial infarction(MI)and its possible mechanism.Methods A rat model of acute MI was created by ligating the left anterior descending coronary artery and administered with Ghrelin within the first week(100 g·kg-1 subcutaneous injection,twice daily for 4 weeks).Cardiac function by echocardiography and cardiac sympathetic nerve activities(SNA)by directly recording cervical sympathetic nerve discharges were measured at 5th week.Myocardial issue from left ventriculus was stained with hematoxylin-eosin and Masson’s to evaluate cardiomyocyte diameter(CMD),cardiac collagen volume fraction(CVF)and infarcted size.The expressions of atrial natriuretic peptide(ANP),brain natriuretic peptide(BNP),and β-adrenergic receptor(β-AR)protein in myocardial tissue homogenate were evaluated by Western blot.Results Five weeks after AMI,rats showed an increased cardiac SNA and developed into chronic heart failure(CHF)with low left ventricular ejection fraction(LVEF)and left ventricular fractional shortening(LVFS)compared with sham group(P<0.01).Ghrelin intervention in the early stage of myocardial infarction significantly inhibited cardiac SNA,narrowed CMD,prohibited cardiac CVF,reduced the expression of ANP and BNP and restored the expression of β1-AR and β2-AR in myocardial tissue from LV(P<0.01).As a result,cardiac systolic function in Ghrelin treated group was significantly improved compared with MI group.Conclusions Early Ghrelin treatment could prevent myocardial remodeling and CHF post-MI,and the mechanism may be related to the inhibition of sympathetic nerve activity and toxicity.Therefore,early intervention of Ghrelin may become a new method for the treatment of heart failure.