促肾上腺皮质激素释放因子介导低氧应激抑制淋巴细胞转化的实验研究

CORTICOTROPIN RELEASING FACTOR MEDIATES LYMPHOCYTE PROLIFERATION SUPPRESSION INDUCED BY HYPOXIA STRESS

本实验以模拟高原低氧方法观察大鼠淋巴细胞对丝裂原（ＣｏｎＡ）的反应性及促肾上腺皮质激素释放因子（ＣＲＦ）介导急性低氧的免疫调节作用。实验结果表明：急性低氧可抑制大鼠外周血淋巴细胞转化，高原土著动物高原鼠兔（Ｏｃｈｏｔｏｎａｃｕｒｚｏｎｉａｅ）则不表现这种低氧抑制作用；肾上腺完整和肾上腺摘除大鼠第三脑室给予外源性ＣＲＦ１μｇ，表现出与低氧作用类似的淋巴细胞转化下降现象；低氧时第三脑室给予高效价ＣＲＦ抗血清可部分阻断低氧抑制作用。放射免疫分析法检测外周血浆中ＣＲＦ和皮质酮水平显示急性低氧大鼠血浆ＣＲＦ、皮质酮水平均升高，高原鼠兔无明显变化。因而，本研究提示：急性低氧可抑制淋巴细胞转化，ＣＲＦ是介导急性低氧抑制淋巴细胞转化的一种因子，而与肾上腺皮质激素的变化可能无关，高原鼠兔免疫功能对低氧不敏感。

Using simulated altitude,the effect of hypoxia on immune function and the mechanisms in-volved in the immune response to hypoxia stress in the rat and altitude native mammal(Ochtonacurzoniae, pika)were studied,The results showed that 5 000m and 7 000m acute hypoxia for 24hin intact rats resulted in 28 % and 4 1 %(P<0.05)decrement in T lymphocyte proliferationrespectively as compared with control group(altitude of 2300m). Similar suppression of immunefuntion in response to acute hypoxia was found in adrenalectomized rats as well,but did not findin pika. Injecton of corticotropin releasing factor(CRF,1μg)into the third cerebral ventricle ofintact and adrenalectomized rats resulted in decrease in lymphocyte proliferation, which was simi-lar to that observed in hypoxia stress.When both intact and adrenalectomized rats were pretreat-ed with icv injection of CRF antiserum,the immunosuppressive effects of acute hypoxia werepartly blocked.An immunomodulatory role of CRF was further supported by the findings thatwhile CRF and corticosterone levels in peripheral plasma significantly increased after acutehypoxia,none of these was observed in pika.The above findings suggest that hypoxia suppressthe immune function and CRF may play a significant role in modulating the immune response toacute hypoxia,probably by adrenal independent mechanisms.The plateau pika presents excel-lent adaptation to hypoxia.