Propofol Post Treatment Improves The Injury And Autophagy Of High Glucose H9C2 Cardiomyocytes Induced By Hypoxia/Reoxygenation By Up Regulating HO-1 Expression

Background: Diabetic patients have a higher risk of myocardial ischemia-reperfusion(I/R)injury and more serious injury than healthy people.Propofol,a general intravenous anesthetic,has been shown to improve inflammation and oxidative stress induced by myocardial ischemia/reperfusion.Recently,it has been found that heme oxygenase-1(HO-1) can significantly reduce myocardial I/R injury by inhibiting oxidative stress and mitochondrial autophagy.However,the relationship between propofol and HO-1 in diabetic patients with myocardial I/R is still unclear.Objective: The purpose of this study was to investigate the effect of propofol on myocardial I/R injury and its potential mechanism in hyperglycemia.Methods: Rat cardiomyocytes(H9C2) were randomly divided into normal group(NC),normal group without hypoxia/reoxygenation(H/R),always cultured in normal glucose medium + 10% fetal bovine serum;hyperglycemia(HG);normal glucose H/R group(H/R);high glucose + H/R group(HG + H/R);25 uM propofol(P);solvent control group dimethyl sulfoxide(DMSO).All cells were cultured in 1 g/L glucose medium and 10% fetal bovine serum medium,and the cell density was controlled at about 50%.HG group was cultured in(4.5 g/L)medium and 10% fetal bovine serum medium for 48 h,then transferred to glucose free and serum-free medium before hypoxia.After 12 hours of anoxia,HG medium + 10% fetal bovine serum was used for 6 hours during reoxygenation.After the study of the effects of propofol on H/R-induced mitochondrial autophagy in HG cardiomyocytes,we carried out another group of studies.In this study,Heme oxygenase-1(HO-1) expression was inhibited by small interference RNA(siRNA),and cells were divided into normal glucose H/R group(H/R);Normal glucose H/R + siRNA group(H/R + siRNA);Normal glucose H/R + adenovirus vector group(H/R + vector);HG + H/R group;HG +H/R + siRNA group;HG + H/R + vector group;HG + H/R + P group;HG + H/R+ P + siRNA group;HG + H/R + P + vector group.To investigate the role ofmammalian rapamycin target of rapamycin(m TOR)signaling pathway(insulin-PI3K-mTOR) in the improvement of H/R-mediated autophagy by propofol post-processing,rapamycin(RAPA),a specific inhibitor of mTOR signaling pathway,was added to the cells in advance,and the cultured cells were randomly divided into P25 group,P25 + siRNA group,P25 + RAPA group and P25 + siRNA + RAPA group.Cell injury,oxidative stress and autophagy levels were compared among groups.Results: 1.Compared with NC group,the injury,oxidative stress level and autophagy level of H9C2 cardiomyocytes in HG and H/R group were significantly increased,and propofol post-treatment could significantly improve the injury induced by HG and H/R(P < 0.05);2.Compared with HG + H/R group,the injury,oxidative stress and inflammation of myocardial cells in HG + H/R + siRNA group increased significantly(P < 0.05),however,HO-1 siRNA reduced the protective effects of propofol on H/R induced injury,oxidative stress and inflammation of HG cardiomyocytes;3.Compared with HG + H/R group,autophagy and apoptosis of cardiomyocytes in HG + H/R + siRNA group increased significantly(P < 0.05),however,HO-1 siRNA reduced the protective effect of propofol on H/R induced autophagy and apoptosis of HG cardiomyocytes;4.Compared with HG + H/R + P25 group,the expression of IGF1 R,p-AKT and p-m TOR in RAPA group decreased significantly,and the autophagy level of cardiomyocytes increased significantly(P < 0.05).Conclusion: Propofol inhibits H/R-induced myocarditis,oxidative stress and autophagy by promoting HO-1-mediated activation of insulin-PI3K-mTOR signaling pathway.