The Effect And Mechanism Study Of Dexmedetomidine On Myocardial Ischemia Reperfusion Injury Through Macrophage Mobility Inhibitory Factor

Objective: The aim of the study is to explore the participation and improvement of energy metabolism,inflammatory response and myocardial cell apoptosis in the process of myocardial ischemia and reperfusion injury(MIRI),to verify that Dex has the effect of preventing and mitigating myocardial injury,and to provide experimental basis and theoretical basis for clinical treatment of MIRI.Methods: The SPF grade C57BL/6 male young mice(4 months old)and aged mice(18 months old)were selected at the animal level,A model of ischemia-reperfusion injury to the myocardium established by ligation of the left anterior descending coronary artery of the murine heart,The expression of IL-6,IL-10,and TNF-α inflammatory cytokines in mouse serum was determined using ELISA;Cardiomyocyte structure and tissue hierarchy were observed by HE staining;TUNEL was used to detect the apoptosis of myocardial tissue;ATP content and ROS to evaluate cardiomyocyte mitochondrial function;Assessment of mouse heart function in an ischemia-reperfusion model using a small-animal ultrasound instrument;Use Western blotting to detect the of MIF,p-AMPK,AMPK,GLUT 4,TLR 4,p-p65,p65,Bcl-2,and Bax protein expression in myocardial tissue;Using transmission electron microscopy to observe the myocardial ultrastructural changes;The myocardial infarction area was measured according to the TTC staining.In clinical trials,patients undergoing coronary artery bypass surgery were selected according to the inclusion and exclusion criteria,and the effects of different doses of Dex on myocardial ischemia and reperfusion injury and the changes in the expression of MIF,c Tn-I and inflammatory factors were observed.Results: In the myocardial I/R model of young mices,IL-6 and TNF-α levels were significantly reduced in the I/R+Dex group(P<0.05),reducing cardiomyocyte necrosis and apoptosis.HE staining showed that the Dex treated group significantly reduced I/R induced myocardial disorder,cardiomyocyte swelling,cardiac fiber rupture,and inflammatory cell infiltmiceion.Cardiomyocyte necrosis and apoptosis were significantly decreased in the I/R + Dex group(P<0.05).The I/R mice had significantly reduced ATP levels in myocardial tissue,while the Dex intervention group significantly improved the energy metabolism disorder.The WB results showed that MIF,p-AMPK,GLUT 4 and Bcl-2 levels increased and Bax levels decreased in the I/R + Dex group.Dex was able to reduce serum IL-6 and TNF-α levels and increase IL-10 levels in the animal myocardial I/R model of I/R mice.Dex can decrease ROS production and apoptosis micee in myocardial tissue,and increase ATP content and MIF expression level.MIF inhibitor(ISO-1)reversed the protective effect of Dex on myocardial I/R injury in mice and reduced AMPK phosphorylation in mice.In the clinical trials of different doses,MIF levels increased in each group,and the high dose group increased greatly,followed by the middle and low dose groups,with significant differences in MIF levels after blocking opening.After blocking,IL-6 was increased in IL-10(P<0.05),but TNF-α did not show statistical difference between the groups.Conclusion: Dex had a protective effect on the myocardium through MIF,and the release of MIF from cardiomyocytes during myocardial ischemia and reperfusion,which activated AMPK and enabled the effective improvement of mitochondrial function.Different doses of Dex can alleviate the oxidative stress response of cardiomyocytes in coronary artery bypass surgery,play a myocardial protective effect,and present a quantitative-effect relationship.