Experimental Studys Of Treatment Of Actue Myocardial Infarction In Rats With Mesenchymal Stem Cells,Hemangiopoietin And Erythropoietin

Myocardial infarction is the leading cause of congestive heart failure and death in developed countries. Despite the development of treatment, methods are limited in preventing ventricular remodeling because of their inability to repair or replace damaged myocardium.Recent observations in the adult heart have suggested that adult cardiac and noncardiac stem cells, may become cardiomyocytes after undergoing natural migration or experimental transplantation into the heart. This evidence indicates that the presence of such cells in the adult extracellular cardiac environment induces the maturation of cardiac phenotypes;thus, stem cell therapy might be effective for regenerating infarcted myocardium.Apoptosis has been implicated as a mechanism that contributes to the loss of cardiomyocytes in chronic heart failure(CHF) and ischaemic injury, erythropoietin (EPO) has anti-apoptotic effects , so it may have beneficial effects on these diseases .HAPO is a novel growth factor acting on the primitive cells of both hematopoietic and endothelial cell lineages and that HAPO may have a clinical potential in the treatment of myocardial infarction.We use Bone marrow mesenchymal cell(BMSC), HAPO and EPO for the treatment of myocardial infarction to investigate their effect on the disease.Method: Part I 60 Lewis rats were randomly divided into 4 groups , every group include 15 rats. We use chloral hydrate(300 mg/ kg) , pentobarbitol sodium (30 mg/ kg)and combined ketamine hydrochloride(25 mg/ kg), pentobarbitol sodium(6.8 mg/kg), atropine(l mg/ kg) with lidocaine(10 mg/ kg) intraperitoneal injection for anesthesia , then we ligate Left anterior descending coronary arteries .after 4 weeks, the cardiac function were evaluated by echocardiography and cardiac catheterization and histologic study were performed alsoPart II 70 Lewis rats were randomly divided into 5 groups , we ligate Left anterior descending coronary arteries to creat myocardiac infarction . Group A (n=15) hemangiopoietin (400ug/kg/day for 10 days) intraperitoneal injection;Group B (BMSC [l×10~7] implantation byleft ventricular intramyocardial injections, n=15);Group C EPO(8000u/kg, n=15) intraperitoneal injection before ligation;. Group D control group (n=15);Group E sham operation group ( n=10). Four weeks after operation , the cardiac function were evaluated by echocardiography and cardiac catheterization. Cardiomyocyte regeneration was testified by immuno -fluerescence and Bcl-2 > Bax, MMP-2 , CD34and MMP-9 were detected by immunohistochemistry. RT-PCR was used to assay mRNA expression of Collagen III, Collagen I and VEGF. Histologic study were performed also.Result: Part I chloral hydrate(300 mg/ kg) is appropriate for anesthesia.Part II Group A> group B and group C have significant reduction in systolic left ventricular diameter(LVDs), diastolic left ventricular diameter (LVDd) and left ventricular end-diastolic pressure(LVEDP), and apparent increase in fractional shortening(FS), ejection fraction(EF), left ventricular systolic pressure(LVSP), the maximum rate of LV systolic pressure rise(+dp/dtmax) and the maximum rate of LV systolic pressure descend(-dp/dtmax) compared with control group(all P<0.05). The apoptosis of cardiomyocytes was significantly inhibited by the transplantation of BMSC and HAPO> EPO intraperitoneal injection (PO.05). Bcl-2 protein expression was evidently up-regulated and Bax protein expression was evidently down-regulated in the group A and group B and group C than that in the control group(P<0.05). The location of labeled BMSC is in belts in group B, and the BMSC can express actin . Hemangiopoietin > EPO can significantly increase mRNA levels of collagen type I(P<0.05), whereas decreased the express of MMP-2(P<0.05). Hemangiopoietin and BMSC can increase the express of .MMP-9(P<0.05). Hemangiopoietin and BMSC and EPO can increase mRNA levels of VEGF and density of capillary vessel. (PO.05).Conclusion: Hemangiopoietin and BMSC and EPO can improve cardiac function in the rat model of myocardiac infarction presumably by acceleration of angiogenesis, inhibition of cardiomyocyte apoptosis and suppression of left ventricle remodeling .