Effect and mechanism of cardiosphere-derived cells in the treatment of rats with acute myocardial infarction ;after reperfusion / 中国基层医药

ABSTRACT

Objective To investigate whether cardiosphere-derived cells (CDCs)can protect ischemia-reperfusion in acute myocardial infarction,and to explore its mechanism.Methods 7 -10 week-old female Wistar-Kyoto (WKY)rats were used for all in vivo experiment.Ischemia was induced for 45 min to allow reperfusion. Twenty minutes (or two hours)later,CDCs (or PBS control)were injected into the LV cavity with an aortic cross-clamp.After 48 hours and 2 weeks,representative echocardiography long-axis images of the left ventricular (LV) systolic and diastolic dimensions,the protein level of activated caspase-3 were observed,the apoptosis rate of myo-cardial cells and the infarct area of the heart were determined in those groups.Results Rats underwent 45 minutes of ischemia,followed by either 20 minutes or 120 minutes (delayed injection)of reperfusion prior to infusion of CDCs (cells per 100μL)or PBS control (100μL)into the LV cavity during aortic cross-clamp.Ejection fraction,as meas-ured by echocardiography,was significantly preserved in CDCs-treated animals at 48 hours with a 20 -minute,but not a 120-minute,delay of infusion(28.0% vs 38.0%,χ2 =7.340,P=0.008).CDCs-treated animals reduced percentage of infarct mass(6.2% vs 13.4%,χ2 =4.226,P=0.002;6.2% vs 13.5%,χ2 =1.853,P=0.003), infarct mass(6.2% vs 13.4%,χ2 =2.220,P=0.002;6.2% vs 13.5%,χ2 =3.119,P=0.003)treated with PBS control.CDC-treated animals reduced infarct size,relative to those of animals treated with PBS control(45.0% vs 24.0%,χ2 =4.825,P=0.008),less thinning of the LV anterior wall(1.96mm vs 1.45mm,t=0.897,P=0.028). Protein expressions of MMP-8 and CXGL7 were elevated in the infarct zone of hearts treated with CDCs(MMP-80.74 vs 0.56,t=0.657,P=0.014;CXGL70.44 vs 0.81,t=0.791,P=0.010).Conclusion CDCs is suggested to be a promising cell source to repair acute myocardial infarction through inhibiting apoptosis and reduce proinflam-matory cytokine expression.