| OBJECTIVE: To investigate myocardiocyte apoptosis with mitochondrial signal transduction activation involved in Myocardial contractile dysfunction in rats with coronary microembolizationMETHODS : 100 adult male Sprague-Dawley rats were randomized to sham-operated group(S group=50) and coronary microembolization group (CME group=50). Coronary microembolization models were produced by injection of 42μm microspheres 0.1ml (3000 microspheres) into the left ventricle during 15 seconds ascending aorta occlusion in rats. The sham-operated control groups were injected saline instead. Each group post ooperation following the time course were randomly into 0h,3h,6 h,12 h,24h five time point groups (n=10) .next following protocol the 6h point of CME was chosen to observation the effect of apoptosis inhibited by Z-VAD-fmk intervention ,another 20 rats were assigned to CME6h group(C group) and the Inhibitor grou(pI group). I group was intravenously infused with Z-VAD-fmk ( widely caspase inhibitor ) 3mg/kg half an hour before CME operation .Cardiomyocyte apoptosis was detected with in TUNEL staining. The activation of bax,bak,bcl-2,bcl-xL,cytochrome C and caspase3 was detected with Western blot analysis. Myocardial contractile function were assessed by transthoracic two-dimensional echocardiography.RESULTS : (1)Compared with control group, the Left ventricular ejection fraction(LVEF)was significally decreased in all CME sub-groups exclude CME0h group(3h:79.18±3.04 % vs 85.53±3.47 %;6h:72.88±3.27 % vs 82.67±3.50 %;12h:68.70±3.82 % vs 84.20±3.51 %;24h:72.11±3.24 % vs 83.50±3.71 % all P<0.05).(2)according with change in contractile function, the apoptosis rate of cardiomyocyte and the levels of actived caspase-3 and bax/bcl-2,bax,bak, cytochrome C proteins were significantly increased in CME group Compared with control group(all P<0.05). the apoptosis index and myocardial Left ventricle ejection fraction(LVEF)had a significant negative correlation(3h group:r=-0.893,p=0.001;6h group:r=-0.856,p=0.003;r12h group::r=-0.964,p=0.002;24h group::r=-0.829,p=0.004),a significant positive correlation was found between apoptosis index and caspase-3,that was also found between caspase-3 activation and bax/bcl-2,cytochrome C proteins .(3) .when with Z-VAD-fmk intervention at 6h after CME, the inhibitor group have a significan improve on myocardial contractile function compared with CME6h untreated group(control group) ( LVEF: 77.96±3.68% vs 72.88±3.27%; CO: 0.162±0.019L/min vs 0.094±0.014L/min; LVEDVd: 5.41±0.32mm vs 6.20±0.16mm; FS: 39.26±2.53% vs 37.59±2.49%),all P <0.05. a significantly decrease of the apoptosis rate of myocardiocyte(0.20±0.11% vs 3.17±1.26% )and the level of activate caspase-3 (0.62±0.30 vs 2.99±1.45) were found after inhibitor intervention.CONCLUSIONS :The increase of myocardiocyte apoptosis were found in rats after CME, with dynamic change in the law. Involve with activate mitochondria—caspase depending signal transduction apoptosis was found to lead to insult of the myocardial contractile function after CME. With the Z-VAD-fmk inhibitor intervention pre-CME, the myocardiocyte apoptosis were decrease and following with an improvement of myocardial contractile function were found after coronary microembolization 6 hours.
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