Propofol Postconditioning Attenuates Hypoxia/Reoxygenation Induced Cardiomyocytes Mitochodrial Damage And Apotosis Via Upregulating FoxO3a Under Hyperglycemia

【Objective】Numerous studies have demonstrated that propofol can significantly ameliorate myocardial ischemia-reperfusion injury in diabetic patients,but its mechanisms have not been fully elucidated.It has been proved that forkhead transcription factor O3a(Fox O3a)can regulate many intracellular biological functions and is related to the progress of various cardiovascular diseases.This study was aimed to investigate the role and mechanism of Fox O3 a in propofol postconditioning mediated attenuation of Hypoxia/reoxygenation injury in H9C2 cells under hyperglycemia.【Methods】H9C2 cells were exposed to high glucose(HG)for 48 hours and then subjected to hypoxia/reoxygenation(the model of H/R injury was established by subjecting cardiomyocytes to 8h of hypoxia followed by 12 h of reoxygenation)in the absence or presence of propofol postconditioning in various concentrations at the onset of reoxygenation.Cell viability,intracellular lactate dehydrogenase(LDH)activity as well as creatine kinase-MB(CK-MB),cardiac troponin I(c Tn I),malondialdehyde(MDA),superoxide dismutase(T-SOD)activity,intracellular adenosine triphosphate(ATP)content and mitochondrial membrane permeability transition pore(MPTP)were measured.Mitochondrial membrane potential and intracellular reactive oxygen species(ROS)were detected by fluorescent microscope.The expression of protein Fox O3 a,Bax,Bcl-2,Cleaved-caspase3,Cytochrome C in cytoplasm were assessed by Western blot.【Results】1.Exposure of cells to HG without or with H/R both significantly increased cell injury,mitochondrial damage,cell apoptosis and oxidative stress and decreased Fox03 a expression(p<0.05).All these changes were further exacerbated following H/R under HG.However,propofol postconditioning can significantly attenuated these injuries with increased Fox03 a expression(p<0.05).The optimal protective effects of propofol was 25 u M.2.These protective effects of propofol were abrogated by Fox O3a-si RNA(p<0.05).【Conclusion】Propofol postconditioning attenuates hypoxia/reoxygenation induced H9C2 cardiomyocytes mitochodrial damage and apotosis via upregulating Fox O3 a under hyperglycemia.