Sevoflurane Postconditioning Regulate Mitochondrial Energy Metabolism Through MIF-AMPK Pathway To Protect Against Myocardial Hypoxia-reoxynation Injury

Subject:In the treatment of ischemic cardiomyopathy,whether it is medical intervention or surgical treatment,the reperfusion of ischemic myocardium will cause damage to the myocardium.Mitochondria are the main energy-supply organelles of cardiomyocytes.When the myocardium is damaged by ischemia and reperfusion,the damage of mitochondria will cause the imbalance of energy metabolism.Previous studies have shown that sevoflurane postconditioning(sevoflurane postconditioning,SpostC)exerts myocardial protection by activating the HIF-1α-MIF pathway,and MIF,as an upstream target protein that regulates AMPK,can protect against myocardial H/R damage by promoting myocardial energy metabolism.This article aims to explore the effect of MIF-AMPK pathway on the energy metabolism of SpostC on myocardial cell hypoxia/reoxygenation injury.Methods: The H/R model of H9C2 cardiomyocytes was established,and the cardiomyocytes were randomly divided into control group,H/R group,H/R+SPostC group,H/R+SPostC+MIF inhibitor group(IOS-1 group).SpostC group was treated with 2.4% sevoflurane at the beginning of reoxygenation.The CCK-8 colorimetric method was used to detect the survival rate of each group of cells;the ELISA kit was used to detect the content of MIF;the dihydroethidine(DHE)staining method was used to detect the content of reactive oxygen species(ROS)in the cells to reflect the degree of oxidative stress of the cells;Use ADP,ATP,acetyl-coenzyme A(AcCoA)kits to determine its content,reflecting the energy metabolism of cells;use qRT-PCR to detect the m RNA expression level of AMPKα gene;use Western blot to determine the protein expression of AMPKα and p-AMPKα Level.Results:(1)SPostC increases the survival rate of cells,reduces the content of ROS in cardiomyocytes,and up-regulates the content of MIF,thereby exerting a cardioprotective effect.(2)H/R cardiomyocytes are damaged,energy metabolism is also weakened,ADP,ATP content is significantly reduced,p-AMPKα expression is also reduced,and the intermediate product AcCoA increases.(3)Compared with H/R+SpostC+ISO-1 group,MIF content,p-AMPKα expression,ADP and ATP content in SPostC group were significantly increased(P<0.05).The cardioprotective effect of MIF-AMPK pathway is related to increased energy metabolism of cardiomyocytes.Conclusion: The SpostC group reduced the generation of ROS by activating the MIF-AMPK pathway,prevented cardiomyocytes from apoptosis,and increased the energy supply of cells after H/R,meeting the needs of mitochondrial energy metabolism,thereby reducing the H/R damage of cardiomyocytes.