The Observation and Analysis of Stem Cell Mobilization and Endogenous Cardiomyocyte Proliferation Promoted by Interval Exercise and Granulocyte Colony-stimulating Factor Using Confocal Microscopy and Flow Cytometry in Myocardial Infarction Rats
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Graphical Abstract
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Abstract
Objectives:To discuss the effects of treadmill interval exercise and granulocyte colony-stimulating factor(G-CSF)on stem cell mobilization,endogenous cardiomyocyte proliferation and cardiac function in rats with myocardial infarction(MI).Methods:90 Adult male sprague-dawley rats were randomly divided into:Sham-operated group(Sham),MI group(MI),MI with interval exercise group(ME),MI with G-CSF treatment group(MG)and MI with G-CSF treatment plus interval exercise group(MGE).The MI model of rats was established by ligation of the left anterior descending(LAD)coronary artery.Rats in ME and MGE groups were subjected to 3-week treadmill interval exercise seven days after myocardial infarction.Rats in MG and MGE groups were injected with rhG-CSF subcutaneously 1h after myocardial infarction,10μg/kg/d for 5 days.Cardiomyocyte proliferation ratio was detected by immunofluorescence and calculated in the peri-infarct region.C-kit and CD29 positive peripheral blood mononuclear cells(PBMCs)were counted by flow cytometer.C-kit and CD29 expression in peri-infarct area was measured by western blot.Hearts were picked for TTC dyeing to decide the myocardial infarction area of each group.Hemodynamic measurement and echocardiography were performed to evaluate cardiac function.Results:Compared to Sham group,the ratio of PCNA and cTnT dual positive cardiomyocytes,c-kit+and CD29~+ cells ratio in the PBMCs,c-kit and CD29 expression in the peri-infarct region,myocardial infarction area were significantly increased and cardiac performance decreased significantly in MI rats;compared to MI rats in periinfarct region,percentage of PCNA and cTnT dual positive cardiomyocytes,c-kit and CD29 positive PBMCs ratio,the expression of c-kit and CD29 protein in the peri-infarct region,cardiac performance were increased significantly,and myocardial infarction area decreased significantly in ME,MG and MGE group.The combined treatment with G-CSF and interval exercise had a better effect than either of them.Conclusions:Interval exercise or G-CSF could promote stem cell mobilization and homing,cardiomyocyte proliferation,cardiac performance and decrease myocardial infarction area significantly in MI rats.The better effects were shown with the combined treatment.
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