Protective Effect And Mechanism Of AMPK-SKP2-H3R17me2 Signal Axis On Hypoxic Preconditioning In MCAO Rats

Objective : To investigate the neuroprotective effect of short term intermittent hypobaric oxygen hypoxic preconditioning on rats after MCAO operation and the role of AMPK-SKP2-H3R17me2 autophagy signal axis in it.Methods :Seventy-two healthy male SD rats were randomly divided into normal control group(NC group,12 rats),sham operated control group(SC group,12 rats),simple hypoxia preconditioning group(HPC group,12 rats),middle cerebral artery occlusion group(MCAO group,18 rats),middle cerebral artery occlusion after hypoxia preconditioning group(HM group,18 rats).Establishment of pathological or physiological model of hypobaric hypoxia preconditioning by using low pressure oxygen chamber to simulate anoxic environment at high altitude.Establishment of pathological Model of Middle Cerebral artery Infarction with modified longa’s Thread Thread Model: to evaluate the neurological function and nerve cell injury,the infarct volume of rats in MCAO group and HM group was measured.Expression of SKP2 protein and H3R17me2 protein in infarct cortex and hippocampus were detected by immunohistochemical method and the expression of H3R17me2 in infarct cortex was detected by western blot.The expression of SKP2 m RNA in infarct cortex and hippocampal ca1 was detected by SKP2 PCR and Elisa method was used to detect the expression of H3R17me2 in infarcted cortex and hippocampal CA1 area.Expression of LC3-II,a molecular marker of autophagy in ca1 region of cortex and hippocampus.Results:The Z-Longa score and the volume of infarction of group HM decreased compared to group MCAO(P<0.05,P<0.05),also,the neuronal damage reduced and the number of remaining neurons increased(P<0.05,P<0.05).In the injured area of cortex and hippocampus(CA1 area),the expression of H3R17me2 decreased(P<0.05,P<0.05),the expression of SKP2 and SKP2 m RNA increased(P<0.05),and the expression of LC3-II decreased(P<0.05).Conclusions:Short term intermittent hypobaric hypoxic preconditioning may inhibit autophagy by inhibiting the activation of AMPK-SKP2-H3R17me2 autophagy signaling pathway,making the autophagy of neurons in the ischemic region not only to a certain extent tolerated ischemic injury but not to cause the death of autophagic neurons,thus protecting the brain tissue of focal ischemic rats.