Effects of propofol on the activation of nuclear factor-kappaB and cardiomyocytes apoptosis during myocardial ischemia/reperfusion injury in rats]

Objective:To explore the molecular mechanisms of propofol in myocardial protection, the activation of nuclear factor-κB (NF-κB) and the apoptosis of cardiomyocytes were examined. Methods: Rat myocardium I/R injury was induced by occluding the left main coronary artery for 30 min and reperfusing 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-κB in the cardiomyocytes was detected by immunohistochemistry. The expressions of NF-κB 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. Results: 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·h) propofol. Compared with the sham control group, NF-κB significantly translocated from the cytoplasm into the nucleus in the I/R group. And the expression of NF-κB in the nuclei markedly increased (P<0.05). In addition, the expression of caspase-3 and the apoptosic 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·h) significantly inhibited the NF-κB translocation into nucleus and attenuated the expression of NF-κB in the nuclei (P<0.05), decreased the expression of caspase-3 in myocardium (P<0.05) and inhibited the occurrence of cardiomyocytes apoptosis. Conclusion: Propofol could inhibit NF-κB activation and down-regulate the expression of caspase-3 and as a result suppress cardiomyocytes apoptotic initation during the myocardium I/R injury, which may be one of the molecular mechanisms of its cardioprotection.