Study On The Mechanism Of HIF-1α/EphrinA1 Signaling Pathway In Diabetic Factors That Impair The Myocardial Protection Of Sevoflurane

Objective:The myocardial protective effect of sevoflurane posttreatment disappeared in diabetic rats with myocardial ischemia-reperfusion injury.The purpose of this study was to investigate whether the loss of cardioprotective effect of sevoflurane is related to the inhibited of the HIF-1α/ ephrin A1 signaling pathway.Methods:Healthy adult male SD rats weighing between 210 g and 260 g.The method of intraperitoneal injection of 50 mg/kg steinbeis-transferzentrum(STZ)combined with high-fat and high-sugar diet for 8 weeks was used to make the type 2 diabetic mellitus(T2DM)rat model.Sixty rats were selected and divided into 5 groups according to random number table method(n=12):Sham operation group,myocardial ischemia reperfusion group(I/R group),sevoflurane post-treatment group(SP group),hypoxia-inducible factor 1α(hypoxia-inducible factor),Factor 1α(HIF-1α for short)activator DMOG group(D group),HIF-1α activator DMOG plus sevoflurane posttreatment group(D-SP group).In the Sham group,the Left anterior descending artery(LAD)was only inserted without blood vessel ligation,while the other groups were ligated with LAD for 30 min.Myocardial ischemia reperfusion injury(MIRI)was induced by 120 min reperfusion.SP group and D-SP group were treated with inhalation of2.5% sevoflurane 5 min before loosening the ligation line for 15 min.D group and D-SP group were intraperitoneally injected with 40 mg/kg DMOG 24 h before operation.At120 min after reperfusion,myocardial tissue was removed,and 4 myocardial specimens from each group were selected by drawing lots.The myocardial infarction area was measured by TTC staining.The remaining 8 rats were divided into 2 parts by taking myocardial tissue below ligation line:Part of them were made into paraffin sections for HE staining to observe the pathological damage of myocardium and immunofluorescence co-localization to observe the position relationship of HIF-1α and ephrin A1.Part of them were used to measure the protein content of HIF-1α and ephrin A1 in myocardium by Western blot.Results:Compared with sham group,the myocardial infarction area and pathological injury were increased,HIF-1α,Ephrin A1 protein expression were down-regulated in the other four groups(P < 0.05).Compared with The I/R group,the myocardial infarction area was decreased,the pathological injury was reduced,HIF-1α,Ephrin A1 protein expression was upregulated in both D and D-SP groups(P < 0.05).There was no significant difference between SP group and I/R group(P > 0.05).The myocardial infarction area in group D was decreased,the pathological injury was reduced,and the expressions of HIF-1α and Ephrin A1 were upregulated when compared with group D(P <0.05).Immunofluorescence co-localization revealed that both HIF-1α and Ephrin A1 were present in the cytoplasm and membrane of myocardial cells,and the two were likely to interact.Conclusion:The loss of myocardial protective effect of sevoflurane may be related to the inhibition of HIF-1α/ ephrin A1 signaling pathway by diabetic factors.