Mechanisms Of Cardiomyocyte Apoptosis Induced By Endoplasmic Reticulum Stress After Coronary Microembolizat

Objective To investigate the dynamic change of cardiomyocyte apoptosis and the role of endoplasmic reticulum apoptotic pathway after coronary microembolization(CME)in rats.Methods Coronary embolization models were produced by injection of 42μm microspheres(3000/0.1ml)into the left ventricle during 10 seconds ascending aorta occlusion in adult male Sprague-Dawley rats(CME group).The sham group was injected saline instead(S group).The survivors were randomly into 3h,6h,12h,24h,4w five groups post CME(n=10).In addition,10 rats were designed as normal control group.Cardiomyocyte apoptosis was detected with in stiu terminal deoxynucleotidyl transferase(TdT)-mediated dUTP nick end-labeling(TUNEL staining).The expression of caspase-12 and procaspase -12 was detected with Western blot analysis.The activity of caspase-12 was determined with caspase-12 fluorometric assay kit.Results(1)Compared with sham-operated group and normal control group,the apoptosis index of cardiomyocytes in CME group were significantly increased at each time point respectively(P＜0.05).Apoptotic cardiomyocytes were found mainly in the border zones and the infarct foci.The apoptosis index ofcardiomyocytes at 3h,6h,12h,24h,4wpost CME were(1.76±0.68) %,(3.17±1.26)%,(1.34±0.12)%,(1.07±0.65)%,(0.30±0.13)%,respectively.The apoptosis index of cardiomyocytes increased at 3h post CME, peaked at 6h post CME(P＜0.05),and then gradually decreased,remarkably low at 4w(P＜0.01).(2)Compared with sham-operated group and normal control group,The relative caspase-12 activation in CME group increased at 3h post CME,peaked at 6h post CME(P＜0.05),and then gradually decreased,remarkably low at 4w(P＜0.01).Significant positive correlation was found between apoptosis index and caspase-12 activation in cardiomyocytes after coronary microembolization in rats.(3h:r=0.806,P=0.024;6h:r= 0.912,P=0.010;12h:r=0.803,P=0.028;24h:r=0.796,P=0.033;4w. r=0.605,P=0.046).(3)Compared with sham-operated group and normal control group,The left ventricle ejection fraction(LVEF)of CME group were markedly decreased(P＜0.05).There was a significantly negative correlation between apoptosis index in cardiomyocytes and LVEF of CME group after coronary microembolization in rats.(3h:r=-0.780,P=0.036;6h:r=-0.862, P=0.013;12h:r=-0.811,P=0.040;24h:r=-0.803,P=0.042,4w:r=-0.675, P=0.040).Conclusions The amount of cardiomyocytes apoptosis was significantly increased after coronary microembolization,with dynamic changes in the law. Endoplasmic reticulum apoptosis 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.