Expression Of HIF-1α In Hippocampus After High Altitude Hypoxic In Rat Model

Objective: To study the expression of hypoxia inducible factor-1α(HIF-1α)in the tissue of hippocampal in the model of high altitude hypoxia in rat.To provided theoretical basis for the brain injury after high altitude hypoxia,and new ideas for the treatment of cerebrovascular disease at high altitude in clinical.Methods: SPF male SD rats(n=35,190-200g)were randomly divided into two groups:(1)Control group: Xining 0-day group(XN 0d group).Rats were airlifted from Beijing(altitude 43.5m)to Xining City,Qinghai Province(altitude 2200m),which took materials directly.(2)High altitude hypoxia model: 1 day high altitude hypoxia group(HY 1d group),4 days high altitude hypoxia group(HY 4d group),15 days high altitude hypoxia group(HY 15 d group),30 days high altitude hypoxia group(HY 30 d group).Rat model of high altitude hypoxia was established by low-pressure simulation chamber(low-pressure simulation chamber setting: altitude 5000 m,oxygen partial pressure 10.4Pa,oxygen concentration 19.6%,temperature 23.3℃,humidity 31.8%,carbon dioxide 300ppm).They were fed for 1,4,15 and 30 days respectively.The morphology of nerve cells in the hippocampal tissues of rats were observed by HE and Nissl staining.The expression of HIF-1α protein in the tissues of hippocampal of rats was detected by the method of Western Blotting.Results: The rat model of hypoxia at high altitude was established by lowpressure chamber successfully.After HE staining,the space around nerve cells in the region of CA1 in hippocampal was widened and cells were swollen in the gourps of HY 1d and HY 4d.While the above morphological changes were slightly alleviated in the groups of HY 15 d and HY 30 d.In the HY 1d and HY 4d groups,neurons in the CA1 area of hippocampal were atrophied and deformed,arrangement disorderly and had some neuron lost.In the HY 15 d and HY 30 d groups,the above morphological changes were slightly alleviated.Compared with the HY 1d group,the expression of HIF-1α protein was significantly decreased in the groups of HY 4d and XN 0d(P<0.05).While the expression of HIF-1α protein was significantly incresased in the groups of HY15 d and HY30 d compared with the groups of HY1 d and HY 4d(P<0.05).Conclusions:(1)The rat model of hypoxia at high altitude was successfully established by low-pressure chamber.(2)After high altitude hypoxia,the expression of HIF-1α protein in hippocampal in the groups of HY 1d and HY 4d were decreased,the space around nerve cells in the region of CA1 in hippocampal were widened,cell swelling,neuronal atrophy,deformation,disorder,and neuronal occurred lost.The expression of HIF-1α protein were increased in the groups of HY 15 d and HY 30 d,which morphological changes were slightly relieved.(3)The expression of HIF-1αprotein was decreased and nerve cells were damaged in hippocampal in the early stage of high altitude hypoxia.It suggested that the expression of HIF-1α protein in the early stage of high altitude hypoxia(1d,4d)was not sufficient to alleviate the neuron damage in the region of hippocampal.The expression of HIF-1α protein was increased and the nerve cell damage was slightly alleviated with the prolonged period of high altitude hypoxia.It suggesed that HIF-1α protein could alleviate the neuron damage in the the region of hippocampal in the late period of high altitude hypoxia rats(15d,30d).