Simulation, 5000 Meters Above Sea Level The Plateau Low Oxygen Environment On Endocrine Of Male C57bl / 6 Mice And The Influence Of Cognitive Function

At the highest point Dome A,antarctic Kunlun station locates at80°25’01"S,77°06’58"E where altitude is4087m and the mean annual temperature-58.4℃with the polar climate of hypoxia and cold.What is more,the oxygen partial pressure is less than the value of sea level about40%,which is equivalent to5000m at low latitude plateau. Our preliminary researches suggested that function of hypothalamic-pituitary-thyroid axis,serum erythropoietin level and cognitive performance of expeditioners were obviously affected in Dome A extreme environment.To explore the mechanism of physiological and psychological changes in extreme environment,we simulated5000m high altitude hypoxia environment by male C57BL/6mice and then study the changes of endocrine and cognitive function which might provide medical basis for diseases prevention of polar expeditioners.Continual hypobaric hypoxia of altitude5000m was administrated for3,7,14and28days separately.The mice were placed in a ventilated and controllable hypobaric chamber.Spatial learning and memory ability was assessed by morris water maze;morphology and structure of thyroid and renal tissue was observed by HE staining,localization and quantitation of thyroid peroxidase(TPO) which is the key enzyme in the synthesis of thyroid hormone and basic protein thyroglobulin (TGB) as well as hypoxia inducible factor HIF-la and HIF-2a were evaluated by immunohistochemistry and western blot;serum levels of FT3、FT、TSH and EPO were measured by ELISA.Section Ⅰ:The effect of simulated5000m high altitude environment on thyroid gland function and cognitive ability of male C57BL/6mice1、Body weight of mice in hypoxia group were significantly lower than control group(p<0.05).2、Compared with control group,morris water maze results showed that lantncy increased after3and28days hypoxia exposure but there was no significant difference.3、There was no significant difference of FT3、FT4and TSH levels between hypoxia and control group,which indicated that the hormone levels of hypothalamic-pituitary-thyroid axis were not affected under hypoxia.4、HE staining results showed that follicles of all hypoxia group were not uniform but quite heterogeneous:different shape and size or colloid density in follicular lumen.Follicular epithelium cells proliferated with flat,prismaticl or cubical.There were more prismaticl or cubical cells than control group.5、Immunohistochemical results showed that HIF-1α and HIF-2α were observed in both normoxic and hypoxia thyroid tissue,which mainly presented in small folliculars.6、Western blot results showed that TGB expression of thyroid tissue in hypoxia group were overall lower than control group.TGB expression level were significant changed after7and28days hypoxia exposure(p=0.016)(p=0.044).TPO expression level when experienced28days hypoxia exposure was significantly higher than that in control group(p=0.015).However, the rest of time point were lower compared with control group and no differences.Although HIF-1α and HIF-2α were observed in thyroid tissue of both groups,the expression of HIF-2α was weaker than HIF-1α(p<0.01).Section Ⅱ:The effect of simulated5000m high altitude environment on erythropoietin of male C57BL/6mice1、As the prolonged of hypoxic exposure,the serum EPO levels in hypoxia group were significantly lower than control group(p<0.05),the minimum at14days and28days recovery.2、EPO is mainly synthesized in kidney.HE staining showed that tubular epithelial cells in hypoxia kidney tissue was hydropic degeneration and tubular was too narrow to be disappeared.Mesangial cells and matrix proliferated meanwhile glomercular capsule stenosis and balloon gap disappeared with interstitial edema.3、Immunohistochemical results showed that EPO and HIF-1α mainly expressed in tubular cells of renal medulla in both normoxic and hypoxia kidney tissue.There was little expression of EPO and HIF-1α in glomerular endothelial cells and mesangial cells in renal cortex.4、Western blot results showed that EPO expression level were significantly increased after7days hypoxia exposure(p=0.024),but decreased at14days (p=0.001).Moreover, HIF-la in kidney tissue of7and28days hypoxia group was significantly higher than control group(p=0.03)(p=0.001).5、The distribution and cellular localization of HIF-1α in hypoxia kidney tissue displayed some overlap with that of EPO.Further studies will be still needed to clarify the mechanism of how HIF-1α regulate EPO expression.