Propofol post-conditioning protects against cardiomyocyte apoptosis in hypoxia/reoxygenation injury by suppressing nuclear factor-kappa B translocation via extracellular signal-regulated kinase mitogen-activated protein kinase pathway

Abstract

Background and objective Perioperative myocardial ischaemia leads to an exceedingly high mortality. Previous studies have indicated that propofol pre-conditioning could mimic the cardioprotective effects of ischaemic pre-conditioning. The purpose of this study was to determine whether propofol post-conditioning is cardioprotective and to explore the possible molecular mechanism of propofol post-conditioning. Methods Primary cultured neonatal rat cardiomyocytes were exposed to 12 h of hypoxia followed by 4 h of reoxygenation (H/R) and post-conditioned by different concentrations of propofol at the onset of reperfusion with and without a specific inhibitor of extracellular signal-regulated kinases (ERKs). Cell apoptosis and the generation of intracellular reactive oxygen species were measured using FACScalibur flow cytometric analysis. ERK1/2 phosphorylation and nuclear factor-kappa B (NF-κB) translocation were determined by western blot and immunofluorescence, respectively. Results Propofol post-conditioning enhanced cell viability (86.6 ± 6.5 versus 64.1 ± 3.4%) and reduced apoptosis (3.6 ± 0.4 versus 12.5 ± 2.1%) to protect cardiomyocytes against H/R injury. Meanwhile, propofol post-conditioning stimulated expression of phosphor-ERKs. H/R markedly induced p65 NF-κB nuclear translocation in cardiomyocytes, whereas propofol post-conditioning significantly suppressed H/R-primed NF-κB translocation. Moreover, addition of the mitogen-activated protein kinase kinase 1 inhibitor U0126 into cardiomyocytes 30 min before H/R eliminated the cardioprotection of propofol post-conditioning. Conclusion Propofol exerts cardioprotection when administered at the early phase of reperfusion. The effect is mediated through decrease in cardiomyocyte apoptosis and NF-κB nucleus translocation potentially via ERK signalling pathways.