Mechanism Of Propofol Alleviating Cobalt Chloride Induced Oxidative Stress Injury In H9c2 Cells By Regulating Glucose Metabolism And Inhibiting Mitochondrial Apoptosis

Objectives:Some studies have found that propofol has protective effect on myocardial oxidative stress response,but its specific mechanism is not clear.Objective to study the oxidative stress（OS）injury of H9c2 cells induced by cobalt chloride（CoCl2）pretreatment with propofol,and elucidate its protective mechanism by regulating glucose metabolism and mitochondrial damage related pathways in H9c2 cells.Methods:The model of OS damage was established by treating H9c2 with CoCl2.H9c2 cells were divided into blank group,injury group（250μg/ml cobalt chloride）,low dose group（propofol 5μM+cobalt chloride 250μg/ml）,medium dose group（propofol 10μM+cobalt chloride 250μg/ml）and high dose group（propofol 20μM+cobalt chloride 250μg/ml）.The apoptotic rate,cell viability,ATP content and intracellular reactive oxygen species（ROS）were detected respectively,which showed that propofol had protective effect on H9c2 cells injured by CoCl2.The glucose metabolism related enzymes 6-phosphate fructose-2-kinase 3（PFKFB3）,pyruvate kinase isoenzyme（pkm2）,monocarboxylate transporter 1（MCT1）,pyruvate dehydrogenaseα1（pdhe1α）and glucose transporter 4 were detected by Western blot The effects of propofol on glucose metabolism and mitochondrial protection in CoCl2injury model were evaluated.The serum levels of interleukin-18（IL-18）and interleukin-1β（IL-1β）were measured by double antibody sandwich ELISA to evaluate the inhibitory effect of propofol on inflammatory factors produced by H9c2cells during oxidative stress injury.Results:We have shown that in the H9c2 cell model damaged by CoCl₂,on the one hand,propofol can improve the survival rate,cell viability and ATP content of H9c2cells,reduce ROS production and inhibit cell apoptosis;on the other hand,propofol increases the expression of PFKFB3,PKM2,MCT1,PDHE1α,GLUT4,and improves glucose metabolism in H9c2 cells under oxidative stress;at the same time,propofol activates Sirt3 The levels of p53,NLRP3 and caspase-1 were inhibited,the release of inflammatory corpuscles was decreased,and the serum levels of IL-18 and IL-1βwere decreased,and the release of inflammatory factors was reduced.Conclusion:Propofol pretreatment can inhibit the oxidative stress injury of H9c2cells induced by cobalt chloride,improve glucose metabolism,and effectively protect mitochondrial function,thus reducing cardiomyocyte apoptosis.