Mechanisms Of Cardiomyocyte Apoptosis Induced By Death Receptor Pathway After Coronary Microembolizat

Objective To investigate the dynamic change of cardiomyocyte apoptosis and the role of death receptor apoptotic pathway after coronary microembolization(CME) in rats .Methods Coronary microembolization models were produced by injection of 42μm microspheres(3×104/ml, 3000) into the left ventricle while occlusion the ascending aorta. The Sprague-Dawley rats were randomly divided into the sham group(S group, n=55), coronary microembolization group(CME group, n=63), The survivors were randomly into 0h,3h,6 h,12 h,24h five groups post CME (n=10). Echocardiography was used to evaluate heart function. Sections of myocardium were stained with hematoxylin-eosin and hematoxylin-basic fuchsin-picric acid for detecting infarct areas. Cardiomyocyte apoptosis was detected with in stiu terminal deoxynucleotidyl transferase (TdT)–mediated dUTP nick end-labeling (TUNEL staining).The expression of caspase-3 and caspase-8 was detected with Western blot analysis.Results The infarct sizes were similar in three hour, six hour, 12 hour, and 24 hour CME groups (P>0.05). The average left ventricle ejection fraction(LVEF) in the normal control group was 87.69±4.41%. Compared with sham-operated group. The LVEF of CME group were markedly decreased( P<0.05 ) expect 0h CME group. Echocardiography showed that Left ventricular ejection fraction(LVEF),short axis fractional shortening(FS) and Cardiac output(CO) decreased, but Left ventricular end-diastolic diameter increased after CME. The apoptosis index in CME group were significantly increased at each time point comparing to sham group(P<0.05) expect 0h CME group, whose peak level showed up at the 6h time point but markedly decreased at the 12h time point. Apoptotic cardiomyocytes were found mainly in the border zones and the infarct foci. The relative expression of caspase-3 and caspase-8 in CME group both increased at 3h post CME, peaked at 6h post CME(P<0.05), and then gradually decreased, remarkably low at 24h. Compared with sham-operated group, the relative levels of caspase-3 and caspase-8 in CME group were significantly increased(P<0.05) expect 0h CME group.Conclusion The amount of cardiomyocytes apoptosis was significantly increased after coronary microembolization, with dynamic changes in the law. Death receptor apoptotic pathway may be involved in coronary microembolization-induced myocardial apoptosis. Cardiomyocytes apoptosis may be one of the important mechanisms of myocardial injury after coronary microembolization in rats.