Effects of propofol on the activation of nuclear factor-kappaB and cardiomyocytes apoptosis during myocardial ischemia/reperfusion injury in rats / 中国应用生理学杂志

ABSTRACT

<p><b>OBJECTIVE</b>To explore the molecular mechanisms of propofol in myocardial protection, the activation of nuclear factor-kappaB (NF-kappaB) and the apoptosis of cardiomyocytes were examined.</p><p><b>METHODS</b>Rat myocardium I/R injury was induced by occluding the left main coronary artery for 30 min and reperfusion for 2 h. Propofol was intravenously given 15 min before ischemia. The pathological changes of myocardium were examined by light and electron microscopy. The translocation of NF-kappaB in the cardiomyocytes was detected by immunohistochemistry. The expressions of NF-kappaB and caspase-3 were determined by Western blot. The incidence of cardiomyocyte apoptosis was detected by the TdT-mediated dUTP nick end labeling (TUNEL) staining.</p><p><b>RESULTS</b>The pathological changes of myocardium induced by I/R injury, such as cardiomyocyte swelling, myofibrillar lysis, disorganized, mitochondrial membrane swelling, and the cristae disruption were significantly alleviated by 6, 12 mg/(kg x h) propofol. Compared with the sham control group, NF-kappaB significantly translocated from the cytoplasm into the nucleus in the I/R group. And the expression of NF-kappaB in the nuclei markedly increased (P < 0.05). In addition, the expression of caspase-3 and the apoptosis index were significantly increased in the I/R group (P < 0.05). Compared with those of I/R group, administration of propofol at 6, 12 mg/(kg x h) significantly inhibited the NF-kappaB translocation into nucleus and attenuated the expression of NF-kappaB in the nuclei (P < 0.05), decreased the expression of caspase-3 in myocardium (P < 0.05) and inhibited the occurrence of cardiomyocytes apoptosis.</p><p><b>CONCLUSION</b>Propofol could inhibit NF-kappaB activation and down-regulate the expression of caspase-3 and as a result suppress cardiomyocytes apoptotic initiation during the myocardium I/R injury, which may be one of the molecular mechanisms of its cardioprotection.</p>