| Background and Objective The medical plateau refers to the environment with an altitude of 3,000 meters above, which can produce biological effects. The hypobaric hypoxic environment can arouse a series of changes among each system from the level of organs to the molecular level, as well as the level from function to structure, including the activation of the hypothalamus-pituitary-adrenal axis (HPA axis). Morever, the changes of light/dark cycle still cause the secretion disorders of the HPA axis hormones. Our groups have found certain hormone secretion disorders among the 29th Chinese Antarctic Inland expeditioners during their residinig at Kunlun station (4.087 meters in height) where the hypobaric hypoxia coupled with the polar day exist. Therefore, this study aims to explore the interaction effect between hypoxia and constant light on activity of the HPA axis, providing scientific data for the polar medicine.Methods The animal model was builded in a simulated 5,000 meters continuous hypoxic coupled with constant light (light intensity 1901ux) environment. The 96 adult male SD rats were randomly divided into four groups:control group (C group), hypoxia group (H group), constant light group (CL group), and hypoxia coupled with constant light group (HL group) and disposed for 2 d,5d and 10d, respectively. The plasma corticosterone and CRF levels were detected using ELISA. Using real-time RT-PCR, the expression of CRF, CRFR1 and CRFR2 genes in the hypothalamic PVN area, as well as the expression of CRFR1 and CRFR2 genes in pituitary were detected. The immunostaing CRF in the hypothalamic PVN area was observed via immunohistochemistry (IHC).Results 1) After exposed for 1 day, significantly reduced food intake (g/d) and body weight (g) were observed among H and HL groups. Among H group, food intake reduced from 20.0g/d (exposed for 0 day) to 1.4g/d, and average body weight decreased from 181.6±15.8g(exposed for 0 day)to 155.0±14.3g(P<0.001, compared with C group)after exposed for 1 day. Among HL group, food intake reduced from 18.8g/d (exposed for 0 day) to 4.0g/d, and average body weight decreased from 185.7±5.6g (exposed for 0 day) to 166.2±6.5g (P<0.001, compared with C group) after exposed for 1 day.2) After exposed for 2 days,5 days and 10 days, respectively, significantly higher plasma CORT and CRF levels were observed among H and HL groups (P<0.01, compared with C group), while no significant changes were observed among CL group. Among H group, the plasma CORT and CRF levels increased gradually with the extension of exposure time(F=21.111, P=0.000; F=5.886, P=0.013); among HL group, they also increased gradually with the extension of exposure time(F=16.739, P=0.000; F=6.389, P=0.010). After exposed for 2 days,5 days and 10 days, respectively, significantly lower plasma CORT and CRF levels were observed among HL group (P<0.05, compared with H group)3) After exposed for 2 days, significantly increased expression levels of CRF in the hypothalamic PVN area, CRFR1 mRNA in the PVN area and pituitary of rats were observed among H and HL groups (P<0.05, compared with C group), while significantly increased expression levels of CRFR2 mRNA in the hypothalamic PVN area and pituitary were observed among HL group (P<0.05, compared with C group). Conclusion 1) Inhibited food intake and reduced body weight were observed after exoposed to 5,000 meters continuous hypoxia and 5,000 meters continuous hypoxia coupled with constant light for 1-10 days.2) The activities of the HPA axis were significantly activated after exposed to 5,000 meters continuous hypoxia and 5,000 meters continuous hypoxia coupled with constant light for 1～10 days, while no significant changes were observed after exposed to constant light (light intensity 1901ux). In addition, the activity of the HPA axis was less activated after exposed to 5,000 meters continuous hypoxia coupled with constant light for 1～10 days than that after exposed to 5,000 meters continuous hypoxia itself.3) After exposed to 5,000 meters continuous hypoxia and 5,000 meters continuous hypoxia coupled with constant light for 2 days, the activation of the HPA axis was closely related to the elevated expression levels of CRF in the hypothalamic PVN area, CRFR1 mRNA in the PVN area and pituitary. Morever, after exposed to 5,000 meters continuous hypoxia coupled with constant light for 2 days, the activation of the HPAaxis was still related to the elevated expression levels of CRFR2 mRNA in the PVN area and pituitary. |
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