Effects Of Hypoxia And Other Stresses On Erythropoietin (Epo) And The Modulation Of NF-κB

Ochotona curzoniae, Microtus oeconomus and Eospalax Baileyi are native mammals resident at Qinghai-Tibetan plateau, and well acclimatized to environmental hypoxia, but the adaptive principle has not been entirely explored. This study reports the effects of hypoxia on Epo expressions in both the prefrontal cortex and the kidney of Ochotona curzoniae, Microtus oeconomus, Eospalax baileyi and mice, and the potential involvement of nuclear factor kappa-B (NF-kB) in mediating the effects of normobaric hypoxia. On the other hand, Epo works as a key regulator of circulating erythrocytes and plays an important role in the growth and development. This study also reports the effects of hypoxia and restraint, along and in combination, on Epo expressions in the kidney of neonatal rats.In the plateau mammal study, hypoxia was simulated by two methods: the cobalt chloride (CoCl₂) treatment and the normobaric chamber. PDTC, an inhibitor of NF-kB, was injected just before the hypoxia exposure in the normobaric hypoxia study. In the neonatal rat study, hypoxia was simulated by hypobaric chamber. Epo protein was determined by Elisa. Results:1. 6 hours after the injection of CoCl₂, Epo in the prefrontal cortex of O. curzoniae (20, 40, 60mg/kg) and E. Baileyi (20, 40mg/kg) significantly increased;M. oeconomus and mice did not respond to CoCl₂ treatment. 6 hours after the injection of CoCl₂, Epo in kidney of O. curzoniae (60mg/kg), M. oeconomus (20, 40, 60mg/kg) and E. Baileyi (20, 40mg/kg) significantly increased;mice did not respond to CoCl₂ treatment.2. Epo expressions in the prefrontal cortex of O. curzoniae and M. oeconomus did not change during normobaric hypoxia (10.8%O₂ or 8.0%O₂);10.8%O₂ or 8.0%O₂ hypoxia significantly enhanced Epo expressions in the prefrontal cortex of mice. Epo expressions in the kidney of O. curzoniae did not change during normobaric hypoxia (10.8%O₂ or 8.0%O₂);8%O₂ hypoxia markedly enhanced Epo expressions in the kidney of M. oeconomus;16.0%, 10.8%O₂ or 8.0%O₂ hypoxia remarkably enhanced Epo expressions in the kidney of mice.3. PDTC treatment during hypoxia had no effects on Epo expressions in the prefrontalcortex of O. curzoniae and M. oeconomus;PDTC treatment during 10.8%O2 or 8.0%C?2 hypoxia significantly reversed the hypoxia-enhanced Epo expressions in the prefrontal cortex of mice. PDTC treatment during hypoxia had no effects on Epo expressions in the kidney of O. curzoniae;PDTC treatment during 8.0%O2 hypoxia significantly reversed the hypoxia-enhanced Epo expressions in the kidney of M. oeconomus;PDTC treatment during 10.8%O2 or 8.0%O2 hypoxia significantly reversed the hypoxia-enhanced Epo expressions in the kidney of mice.4. Epo expressions in the kidney of 35-day-rats are significantly higher than 63-day-rats. Hypoxia, restraint and their combination markedly decreased Epo expressions in the kidney of 35-day-rats;prenatal stresses have more obvious effects than postnatal stresses;restraint has more obvious effects than hypoxia. Hypoxia, restraint and their combination markedly increased Epo expressions in the kidney of 63-day-rats;postnatal stresses have more obvious effects on kidney Epo than prenatal stresses.Conclusions:1 . Ochotona curzoniae, Microtus oeconomus and Eospalax Baileyi are well acclimatized to environmental hypoxia. Ochotona curzoniae and Microtus oeconomus might be de-sensitive or have high endurance to hypoxia;hypoxia had smaller effects on their Epo expressions in both the kidney and the prefrontal cortex. In contrast, Eospalax Baileyi adapts to hypoxia through activating Epo expressions rapidly and efficiently. These differences might be caused by their different living environments or the differences of their species.2. Epo expressions were induced by normobaric hypoxia through NF-kB mediation in both the brain and the kidney.3. Epo expressions in the kidney of 35-day-rats are significantly different from 63-day-rats. Hypoxia, restraint and their combination markedly decreased Epo expressions in the kidney of 35-day-rats, but markedly increased Epo expressions in the kidney of 63-day-rats.