To Study The Research Of The Relationship Of Receptor Of Advanced Glycation End Products And Cardiac Ischemic Reperfusion Injury

Background:With the improvement of living standard, the prevalence of coronary atherosclerosis heart disease (coronary heart disease)and the mortality rate is on the rise, and the main factor of its pathogenesis is myocardial ischemia.To decrease the infarct size and restore cardiac function after acute ischemic events, an early and effective implementation of myocardial reperfusion is important. After reperfusion therapy, ischemic myocardium may induce arrhythmia, myocardial diastolic dysfunction, metabolic abnormalities and the changes of myocardial micro structure. This is called "myocardial ischemia reperfusion injury (MIRI)". Therefore, one of the most important research is how to reduce and prevent myocardial ischemia-reperfusion injury. Many studies have shown that ischemic preconditioning (IPC) can protect myocardial cells, reduce myocardial ischemia-reperfusion injury, but the occurrence of myocardial ischemia is highly unpredictability and hence its application has some limitations. In recent years, several researchs have shown that distal limb ischemia-reperfusion (I/R) can improve the tolerance of myocardial ischemia-reperfusion injury and also reduce myocardial ischemia reperfusion injury, this is known as the ischemic postconditioning (IPOC).Receptor advanced glycation end products (RAGE) is a transmembrane protein member of the immunoglobulin superfamily, which has many ligands, including advanced glycation end products(AGEs), S100/calcium of members,high-mobility group box-1. Soluble RAGE (soluble RAGE, sRAGE) is one of the C terminal shear body of RAGE, the shear body may combine with ligands or through replacement of full length protein level to regulate of RAGE.Some literature reported that RAGE Played an important role in cardiac ischemia-reperfusion injury. RAGE express increase after Ischemia reperfusion therapy. Blocking RAGE ligands axis, ischemia-reperfusion injury alleviate. Previous studies showed that IPOC has a protective effect on ischemia-reperfusion injury. However, the protection of IPOC on myocardial ischemia-reperfusion injury is unkown.Objective:To investigate the role of RAGE and the mechanisms of the remote ischemic postconditioning to myocardial ischemia reperfusion injury.Methods:(1) 48 patients of jiangsu province people’s hospital who were treated with percutaneous coronary interention menstruation (PCI) in Geriatric cardiology, were randomly divided into two groups:group one comprising of patients only percutaneous coronary interention menstruation (PCI) and group two comprising of patients with percutaneous coronary interention menstruation (PCI) plus distal ischemic post conditioning. Blood was drawn from the patients of both group just mintutes before PCI,6 hours after PCI,12 hours after PCI,24 hours after PCI. hscTnT levels in serum were determined with Roche automatic electrochemical luminescence instrument, Enzyme-linked immunofluorescence (ELISA) test was used to determine the levels of sRAGE, HMGB1, IL-6 in serum.(2) 39 adult mice(C57BL/6J) were randomly divided into three groups:sham, ischemic/reperfusion(I/R) and distal ischemic post conditioning(IPOC). All the mice in each group underwent open-chest surgery, the I/R group mices underwent left coronary artery (LCA)occlusion and reperfused surgery. In IPOC group, three cycles of 3 min distal ischemic followed by 3 min distal reperfusion were performed in the early stage of myocardial reperfusion. The hemodynamic indexes(EF%、FS%) were measured after 24h using animal ultrasonography. The infarct size was measureed, the ratio of the infarct size was measured by TTC staining and ischemic size by evans blue. The expression of RAGE, HMGB1, AKT, ERK were observed after 2 hours by Western Blot.Results:(1)In patients undergoing PCI, befor PCI between distal ischemic post conditioning treatment group and control group of only percutaneous coronary interention menstruation (PCI), serum hscTnT、HMGB1、IL-6 were increased.There was a decreased in serum levels of sRAGE (P<0.05).12 hour after PCI,in treatment group compared with the control group,serum hscTnT 、HMGB1、 IL-6 were decreased and elevated serum sRAGE levels (P<0.05)(2)After 24h reperfusion in ischemic myocardium, LVEF (%)、LVFS (%) (P<0.05) which were hemodynamic parameters and myocardial infarction area (P<0.05) were improved.Compared with only ischemia-reperfusion group,the group of after 2h reperfusion in ischemic myocardium plus ischemic post conditioning,RAGE(P<0.05),HMGB 1 (P<0.05)expression level were significantly reduced,P-AKT (P<0.05) was increased.Conclusion:Distal ischemic post conditioning improves cardiac dysfunction, reduces myocardial infarction which has been caused by ischemia-reperfusion injury. The combination of RAGE and HMGB1 could be involved in this process.