The Effects Of High Altitude Acute Hypoxic Exposure On Rat HPA Axis And The Interfered Mechanisms Of The Drugs

Objective:1. To compare the influence on different simulated altitude and different hypoxic time of HPA Axis. And to explore the regulation hormone secretion of HPA axis in different hypoxic conditions and degree of damage produced by anoxia.2. To explore the influence on plateau hypoxia rats by the intervention of HPA axis drugs,(mifepristone, dexamethasone, metyrapone) and explore the key point of hormone secretion of HPA axis.3. To study the influence on the hypoxia rats by the intervention of epimedium flavonoids and to explore the traditional Chinese medicine composition of effective treatment to plateau anoxia.Methods:1. The hormone level of HPA axis in serum is measured by simulating altitude of5000m.7000m, and hypoxic exposure to12hours, including serum CRH, ACTH, CORT, Anoxia levels of rats including BUN,MDA, LDH levels in serum is detected. Serum CORT and LDH levels are detected by simulating altitude of5000m and hypoxic exposure to8hours,12hours,24hours and48hours.2. Serum CRH, ACTH,CORT and S100B level is detected through giving the interfered drug of HPA axis including dexamethasone, mifepristone and metyrapone by simulating altitude of5000m,7000m, and hypoxic exposure to12and24hours. Brain and lung tissues are extracted and their water content are measured.3. The rats which were given EpimediumTotal Flavonoids were divided into three dose groups,that is high dose of710mg/kg, medium dose of305mg/kg and low dose of150mg/kg. once per day,and all seven days.Dexamethasone was used as positive compared group. The dose is0.5mg/kg. simulated altitude of5km, hypoxic exposure to72hours. The level of SOD, MDA, TNOS, iNOS and NO in serum and brain, lung, heart tissues were measured, the level of S100B and CORT in serum and brain tissue are detected;t brain and lung tissues are extracted and their water content were detected.Results:1. The three main indicators hormone of HPA axis (CRH, ACTH, CORT) increased with the increasing of altitude (P<0.01), the CORT increased swiftly and with the time extension, it gets to peak at24hours BUN, MDA increase with the increasing of altitude (P<0.01), as the altitude rises, the LDH decreased (P<0.01)2.(1)Compared with the plain group, CRH, ACTH, CORT of the control plateau group in serum were significantly increased (P<0.05), CRH, ACTH, CORT level in dexamethasone group increased significantly (P<0.01), CORT level in mifepristone group increased significantly (P<0.05), ACTH level in metyrapone group increased significantly (P<0.01); Compared with plateau control group, CRH level, CORT level in dexamethasone group increased significantly (P<0.01), ACTH level in mifepristone group decreased significantly (P<0.01).(2) Compared with the plain group, CORT, S100B, brain water content and pulmonary water content in other groups were significantly increased (P<0.01); compared with plateau control group, CORT in dexamethasone group increased significantly (P<0.01), S100B level decreased significantly (P<0.05), CORT level of mifepristone group decreased significantly (P<0.01), S100B levels increased significantly (P<0.01), the brain water content were increased, but there was no significant difference.water content in lung tissue of metyrapone group decreased significantly (P<0.05).3. Compared with the plain group, CORT, SOD, TNOS, NO in serum, brain, lung, and heart tissues were significantly increase of high dose of epimedium group; MDA decreased significantly; in dexamethasone group, CORT in serum, TNOS in brain, lung, iNOS in brain, heart were significantly increased, S100B, iNOS in serum, NO in brain tissue were significantly lowed, water content in brain tissue between plateau groups increased,but there was no significant difference, water content in lung tissue plateau groups were significantly increased (P<0.01). Compared with the plateau control group, the content of CORT SOD, TNOS, NO in serum and brain tissue of high dose of epimediume significantly increased, CORT, SOD, TNOS in serum and TNOS brain, lung tissue,NO in heart tissue of dexamethasone group increased significantly, S100B in serum, MDA in serum, heart, lung tissue decreased significantly, water content of brain in dexamethasone group decreases, but there was no significant difference.Conclusion:1. When the organism were exposured in acute hypoxia, HPA axis will excited, accompanied by the increase of elevation, the secretion of CRH. ACTH.CORT will increase. Low oxygen activation of HPA axis. CRH plays a key role in the reaction of HPA axis during hypoxia.2. The same height, different oxygen time, the excited secretion of CORT from HPA axis of rats has changed over time, CORT increased accompanied by time extended, during acute anoxia; reached in peak at24hour.3.(1) Plateau during acute hypoxia, stimulate the function of HPA axis.the secretion of CRH increase, then the secretion of ACTH,CORT increased, dexamethasone promote the releasing of corticosterone from adrenal cortex, At the same time, S100B and water content of the brain reduced, which were inhibited by metyrapone in some degree.(2) Comparison shows that the increasing of corticosterone has protective effect on hypoxia brain damage of rats during acute severe hypoxia, and its mechanism may be related to down-regulation of S100B and stable blood brain barrier.4. Epimedium total flavonoids has a protective effec on Anoxic damage in rats, its high dose (710mg/kg) is the most effective, can improve different the level of SOD, NOS and NO in serum brain, lung, and heart tissue, reduce the level of MDA, increase the level of CORT from the terminaof1HPA axis,the The above conclusion show that total flavonoids of Epimedium has good development prospect in anti-hypoxic.