| Background and ObjectiveMI (myocardial infarction) is one of diseases which badly threaten human health with death at present. Because adult cardiomyocytes have severely limited capacity to regenerate, there will be much more loss of cardiomyocytes after AMI hopelessly, which would be replaced by scar tissue. This procedure will lead to heart failure. If we find some methods to reduce the loss of dead cardiomyocytes the furthest, promote stunning and hibernating myocardium function recovery, enhance ischemic neovascularization and supply the infarct myocardium with cardiomyocytes regeneration, we can inhibit the formation of myocardial scar and reduce the degree of ventricular remodeling to improve the heart function for grave myocardial damnification and heart failure. Several studies suggest that transplantation of embryonic stem cell or adult stem cell can repair the injured myocardium and improve the heart function, especially EPCs(endothelial progenitor cells). Evidences suggest that transplantation of bone marrow-derived or peripheral blood-derived EPCs can enhance ischemic neovascularization. The survival and differentiation of the transplanted cells is mostly determined by the local microenvironment and their ability .so if we can improve the local microenvironment and inforce the ability of EPCs, the transplanted cells would produce much more beneficial. Several studies have demonstrated that Statins possess the pleiotropic effect independent of cholesterol reduction, which include inhibition of inflammatory responses, improvement of endothelial dysfunction and enhancement of EPCs' ability. Using the pleiotropic effect of Statins which would bring the beneficial effect to EPCs, this study is to investigate the repair function and the mechanism of injured myocardium with Statins plus EPCs in acute myocardial infarction.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 Three groups by random,10 rats in every group:the control group(group I );EPCs transplantation group(group II); EPCs transplantation plus atorvastatin group(group III). Rats were anesthetized with chloral hydrate, then they were fixed on the operation table in dorsctle position. We extracted 3ml 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 and groupIII 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 groupIII were lavaged with atorvastatin at dose of 50mg/kg/d. 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 atorvastatin 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 atorvastatin 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 atorvastatin group(p<0.05), they were more prominence in EPCs transplantation plus atorvastatin 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 and EPCs transplantation plus atorvastatin 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 BrdU labeled EPCs 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 improve the heart function through neovascularization. It indicated that EPCs can repair the ischemic myocardium obviously.(3) EPCs transplantation plus atorvastatin 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 at two aspects of constriction and diastole obviously. The effect is priors to EPCs transplantation lonely.
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