A Study Of The Decreasing Myocardial Necrosis And Limiting Left Ventricular Remodeling By EHGF And Its Mechanism After AMI

Hepatocyte growth factor is a mesenchyme-derived pleiotropic and potent mitogen factor that regulates cell growth, motility and morphogenesis of various types of cells, and plays a key role in tissue formation, live and kidney regeneration, wound healing, embryo development and tumor metastasis. Recent study indicated it also is a kind of cardiotrophin, but its cardioprotective mechanism is still unclear. The purposes of our study were to investigate the effect of exogenous HGF on impaired myocardium and its probable mechanism after AMI.Method: Rabbit model ligated proximal left anterior descending coronary artery (LAD) was used. Animals in sham-operation and control groups were intravenously infused nomal saline, and in experimental group were given HGF(2mg/kg.12h). 1. After LAD ligated 2days, hemodynamic studies were performed in each group by echocardiogram, and ischemia area and infarcted size were also measured. Cell apoptosis was detected by TUNEL straining, and expression of bcl-2 proteins was analyzed by immunohistochemistry. The expression of ERK1 and pERK1 were measured by western blot. 2. After LAD ligated 4 weeks, both hemodynamic studies and the indexes of ventricular remodeling were performed in each group by echocardiogram. Ischemia area and infarct size were also measured by triphenyltetrazolium chloride staining. Cell apoptosis was detected by TUNEL straining, and capillary density was counted by immunohistochemistry using a monoclonal anti-CD31 antibody. Results: 1.1 The infarct size in experimental group was significantly less than that in control group(31.72%±6.62%vs14.08%±4.63%; P＝0.002<0.01), and left ventricular function was improved; 1.2,myocardial apoptotic index of experimental group was significantly lower than that of control group(57.75‰±7.50‰vs33.25‰±5.32‰ P=0.02<0.05); 1.3, Exogenous HGF could promote the expression of bcl-2 proteins. The expression of ERK1 was not found different between groups, but the expression of pERK1 in experimental group was increased significantly compared with that in control group. 2,Compared with sham-operation group, control group had a higher left ventricularend-diastolic volume, left ventricular weight and left ventricular wall thickness (P<0.05~ 0.01),and had a lower FAS and EF. LVESV,LVEDV were significantly decreased, and FAS and EF were significantly increased in experimental group as compared with control group. Cell apoptotic rate and infarct size in experimental group were significantly lower than that in control group. Left ventricular diameter was positively correlated with cell apoptotic rate. Capillary density in experimental group was significantly higher than that in control group. Conculsion: 1,Exogenous HGF can decrease infarct area, apoptotic rate in cardiomyocyte, limit the left ventricular remodeling and improve left ventricular function. 2,The cardioprotective roles are probably associated with promoting the expression of antiapoptotic bcl-2 proteins and angiogenic property of eHGF. 3,As one of signal transduction pathways, phosphorylation of ERK1 is assiocated with the cardioprotective role of HGF.