| Background and ObjectiveCoronary artery disease especially Acute Myocardial Infarction is a worldwide health problem since the 20th centrury. With the changing of life styles, the morbidity and mortality is increasing in developing countries including our country.Abrupt occlusion of coronary arteries causes AMI, which leads to massive cardiomyocyte loss and consequently deterioration of cardiac function because cardiomyocytes have severely limited capacity to be divided and thus replace the damaged tissue. Progressive heart failure is a major cause of death or frequent hospitalization in patients after MI. Although MI is classified as vascular (coronary artery) disease, therapeutic strategies should be focused on regenerating not only blood vessels but also cardiac muscle to improve the poor prognosis of the disease.Compelling evidence suggests that transplantation of bone marrow-derived CD34~+cells or cultured EPCs(endothelial progenitor cells)-enriched population contributes to preservation of LV function after MI through enhancing ischemic neovascularization. The mechanism of this therapeutic effect was previously considered to be incorporation, differentiation, and proliferation of EPCs for new blood vessel formation. Recently,people reported in vitro transdifferentiation of EPCs into functional cardiomyocytes. And also demonstrated in vivo differentiation of CD34~+cells into cardiomyocytes and smooth muscle cells (SMCs) in a mouse model of acute MI. Regeneration of SMCs as well as ECs may result in mature vasculogenesis, which is more potent for blood flow recovery in ischemic myocardium compared with capillary formation by EC-only regeneration. These findings lead to a novel concept that EPCs transplantation may contribute to cardiomyogenesis and vasculogenesis, which maybe an ideal strategy to treat MI.Although we doing well in the EPCs transplantation therapy, but there are still some localizations .Improvement of heart function is determined by the survival and differentiation of the transplanted cells. If we can improve the local microenvironment,restrain inflammatory reaction,reduce apoptosis and inforce the survival ability of EPCs during the time of cellur transplantion.This study is to investigate the feasibility and therapeutic effect by using fenofibrate and thiazolidindiones plus EPCs to cure AMI.And through this study we expect to explore the cardiovasclur protection of fenofibrate and thiazolidindiones except to regulate adipocyte differentiation and glucose homeostasis.MethodsTo take male Sprague-Dawley (SD) rats (weight between 150-200 gram) from animal experimental center of the medical college of zhengzhou university as studied object and feed on normal diet. male SD rats were divide into four groups by random, 10 rats in every group:the control group(group I );EPCs transplantation group(group II );EPCs transplantation plus fenofibrate group(group III );EPCs transplantation plus Rosiglitazone group(groupIV).Rats were anesthetized with chloral hydrate, then they were fixed on the operation table in dorsctle position.We extracted 3 ml blood from the heart,using heparin anticoagulatiom. Mononuclearcells were collected by density gradient centrifugation.The EPCs were purified by culture and expanded in vitro and labeled with BrdU.AMI was induced by ligating the left anterior descending coronary artery.After AMI rats from group II,group III and groupIV received intramyocardial transplantation at six different spots in the infarct perimeter areas,and with 50μl in every spot.Rats from group I were intravenously injected with equal dose of culture medium .After twenty-four hours,rats from group III and group IV were lavaged with fenofibrate at dose of 20mg/kg/day and Rosiglitazone at dose of 4mg/kg/day difference.Echocardiogram was used to detect their effects on heart function and eight-leads physiological recording machine was used to mensurate dynamic index after eight weeks. Then executed rats, Examined EPCs in myocardium by immunohistochemical staining.Result(1)After eight weeks of myocardium infarction,echocardiography indicated that the heart function had a great improvement in EPCs transplantation group,EPCs transplantation plus fenofibrate group and EPCs transplantation plus Rosiglitazone group. Left ventricular cubage, ejective fraction (EF) , Left ventricular franctional shortening(FS) all had a great improvement compared to the control group(p<0.05), and that they were more prominence in EPCs transplantation plus fenofibrate group and EPCs transplantation plus Rosiglitazone group(p<0.05).(2)The dynamic results indicate that compare to control group, left ventricular systolic pressure (LVSP) and the±dp/dt max had a great improvement and left ventricular end-diastolic pressure ( LVEDP ) had a great decrease in EPCs transplantation group,EPCs transplantation plus fenofibrate group and EPCs transplantation plus Rosiglitazone group(p<0.05), they were more prominence in EPCs transplantation plus fenofibrate group and EPCs transplantation plus Rosiglitazone group(p<0.05). It indicated that the heart function had improved at two aspects of constriction and diastole.(3) Eeight weeks after transplantation, the BrdU labeled EPCs could be found at the areas of infarction in EPCs transplantation group,EPCs transplantation plus fenofibrate group and EPCs transplantation plus Rosiglitazone group. There were new vessels raised by incorporation of EPCs after transplantation.It indicated that the transplanted cells had been live in infracted areas and had participated in the process of neovascularization.There were no neonatal myocardial cells in control group and the infarct areas' fibrosis was obvious.Conclusion(1) In this experimental we indicated that mononuclear cells can been collected by density gradient centrifugation from peripheral blood, and the EPCs can separate, purify and cultivated.(2) Intramyocardially transplanted of EPCs to the infarcted myocardium after AMI, EPCs can regeneration of infarcted myocardium and enhance neovascularization. And significant to improve and preserved left ventricular (LV)function of the rats.(3) EPCs transplantation plus fenofibrate group and EPCs transplantation plus Rosiglitazone group can improve the existent microenvironment of transplanted cells remarkably and promote more transplanted cells alive, reduce infarct areas, restrain ventricles reconstitution and improve the heart function obviously. The effect is priors to EPCs transplantation lonely.
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