Ghrelin对心梗后心衰大鼠心功能的影响及机制研究

Effect and Mechanism of Ghrelin on Heart Failure after Myocardial Infarction in Rats

目的阐明Ghrelin对心梗后心衰大鼠心功能的影响及其相关机制。方法采用结扎左冠状动脉前降支构建心梗后心衰大鼠模型,并在术后将动物随机分为模型组和Ghrelin治疗组,并设立假手术组对照。术后第5周开始皮下注射Ghrelin,连续给药4周。通过血流动力学检测及心脏超声检查评价心功能,HE染色观察心肌重构,TUNEL染色观察心肌细胞凋亡情况,并应用ELISA检测血管紧张素II(Ang II)水平。结果与假手术组相比,模型组大鼠的左室舒张末压(LVEDP)明显增加,左室收缩末压(LVSP)与射血分数(EF)明显下降;心肌细胞凋亡数明显增加,心肌重构显著;AngⅡ水平明显增高。与模型组相比,Ghrelin治疗组LVSP及EF显著提高,LVEDP显著降低;心肌细胞凋亡数目明显减少,心肌重构减轻;AngⅡ水平明显下降。结论 Ghrelin可抑制心肌细胞凋亡改善心肌重构,进而提高心衰大鼠心功能,其机制可能与Ghrelin下调Ang II抑制肾素-血管紧张素-醛固酮系统(RAAS)的激活有关。

Objective To clarify the effect and possible mechanism of ghrelin on heart failure（HF）after myocardial infarction（MI）.Methods The rat model of heart failure was induced by ligating the left anterior descending（LAD）of female Wistar rats,and the animals were randomly divided into the model group（MI）and the ghrelin treatment（MIGhrelin）group after the operation,and the sham operation（SO）group was compared.In the 5th week of surgery,ghrelin administered by subcutaneous injection for 4 weeks.Then,the cardiac function was assessed by LV end-diastolic pressure（LVEDP）,left ventricular systolic pressure（LVSP）,± dp/dt max（mmHg/s）and ejection fraction（EF%）.Hematoxylin and eosin（HE）staining waw used to analyze the morphological changes in the myocardium and TUNEL assay was performed to detecte myocardial apoptosis.In addition,the serum and non-infarct myocardial tissue angiotensin II（Ang II）were measured using ELISA.Results Compared with the sham group,the number of myocardial apoptosis,the LVEDP and of model group increased significantly（P〈0.05）,the LVSP,EF and the level of Ang II were decreased significantly（P〈0.05）.However,ghrelin could significantly increase the EF and LVSP,decrease the LVEDP,reduce the number of cardiomyocyte apoptosis,and down-regulated the expression of Ang II.Conclusion By down-regulating the Ang II expression in myocardial cells in rat HF after MI,ghrelin treatment decreased the apoptosis of myocardial cells,suggesting the possible mechanism by which ghrelin functions in protecting against heart failure.