| Objective:To screen the anti-hypoxia active components of Epimedium Herb(HE),study the anti-hypoxia pharmacological effect and explore its mechanisms.Methods:The anti-hypoxia active component of Epimedium Herb was screened by the closed anoxic model under the condition of ordinary.The mechanisms of its effect were studied by the low pressure and immunization models in mice,respectively.The mechanism of the active components of HE was investigated by the acute anoxic model under the low pressure conditions similar to the plateau hypoxia environment in BALB/C mice,and according to the purpose of the experiment,the mice were divided into four groups,i.e.normal control group,HYM group,drug-treated group and positive control group.All drugs were administered by intragastric administration(i.g.).The mechanism of the active components of HE was systematically evaluated by determining the following indicators.The content of water in cerebral,myocardium and lung tissues;SOD activity,lactic acid,malondialdehyde(MDA) and protein content in both cerebral and cardiac tissues;liver glycogen and muscle glycogen contents,GK and G-6-P activities in liver;levels of plasmatic corticosterone,plasma glucose level and plasmatic testosterone,estradiol peripheral hemogram and organ index;pathological sections of cerebral, myocardium,adrenal and testis tissues.The mechanism of the active components of HE was also studied by the protective effects on heart,brain and lung,the regulatory effects on glucose and protein metabolism,and the improving effects on nerve-endocrine-immune system. Results:The survival time of mice under ordinary pressure was longer in aqueous extracts of Epimedium Herb treated groups than that of blank control group(P＜0.05).TFE had a similar effect on increasing the survival time of mice than that of aqueous and alcohol extracts of HE. The mice treated with the high-dose of TFE(900 mg·kg-(1)·d-(1)) displayed the longest survival time.The treatment of TFE significantly increased the contents of red blood cell,white blood cell and lymphocytes,and the hemoglobin content as well.In the dose-effect relationship study of TFE anti-hypoxia,high-dose of TFE(900 mg·kg-1·d-1) showed the most significantly increasing effects.After the administration of TFE,SOD activity increased,while MDA and lactic acid content decreased in cerebral and cardiac muscle tissue.Meanwhile,plasma glucose level,the liver G-6-Pase activity and protein content in both cerebral tissue and cardiac tissue increased,while liver glycogen content,GK activity and the content of water in cerebral tissue,myocardium and lung tissue decreased when the mice were exposed to hypoxia.The pathological study proved that there was some damage in cerebral and cardiac muscle tissue,which was protected by the treatment of TFE in hypoxia mice.Compared with hypoxia model group,after the administration of TFE,the function of HPA axis was inhibited,the level of plasma corticosterone decreased and organ index of adrenal increased in hypoxia stress mice.The pathological study proved that there was some damage in adrenal tissue,which had been protected by the treatment of TFE in hypoxia stress mice.TFE was also proved to have the effect similar to sex hormone.After the administration of TFE,the function of HPA axis was regulated,the content of plasma estrogen and testosterone increased.The pathological study also demonstrated that testis tissue was damaged while protected by treatment of TFE in hypoxia stress mice.Compared with hypoxia model group,TFE increased immune organ index,leukocyte and lymphocyte numbers of immunosuppressive mice induced by cyclophosphamide.High-dose ofTFE(900mg·kg-1·d-1) had the best anti-hypoxia stress effect among the three groups. Conclusion:Epimedium Herb has significant anti-hypoxia pharmacological effect.TFE is the active components of Epimedium Herb in the antihypoxia effect.On the reasonable range of dosage,it showed linear dose-effect relationship.TFE can improve the metabolism of free radical,water and salt content in cerebral and cardiac muscle tissues.It can also reduce edema degree,and thus plays an important role in the protection for cerebral,cardiac and lung in hypoxia mice.TFE can also regulate the metabolism of substance,increase the speed of glucose metabolism,slow down protein metabolism and increase the fasting blood glucose level to supply energy to critical organ protecting the heart and brain of hypoxia mice.TFE had inhibitory effect on HPA axis of hypoxia mice.It acted as a sex hormone for the regulation of HPG axis function and could improve the immune function of immunosuppressive mice induced by cyclophosphamide,suggesting that TFE reduced injury ofhypoxia mice by the mechanism of NIM.TFE can improve blood component,increase the oxygen-carry ability of blood,the number of white blood cell and lymphocyte cell and the immunological competence in hypoxia stress mice.Hence,TFE effectively improve the functions of humoral immunity and nonspecific immuuity.
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