Niess A M, Fehrenbach E, Lorenz I, Müller A, Northoff H, Dickhuth H-H, Schneider E M
Medical Clinic and Polyclinic, Department of Sports Medicine, University of Tuebingen, Germany.
J Appl Physiol (1985). 2004 Mar;96(3):1231-5; discussion 1196. doi: 10.1152/japplphysiol.00803.2003.
Recent research has demonstrated that reactive oxygen species (ROS) participate in intracellular signaling processes initiated during hypoxia. We investigated the role of ROS in the response of plasma erythropoietin (Epo) to short-term normobaric hypoxia in humans. Twelve male subjects were exposed twice to 4 h of normobaric hypoxia (H; inspired oxygen fraction 12.5%) with a period of 6 wk between both experiments (H1 and H2). With the use of a randomized placebo-controlled crossover design, the subjects received orally a combination of the antioxidants all-rac-alpha-tocopherol (800 mg/day for 3 wk) and alpha-lipoic acid (600 mg/day for 2 wk) or placebo before H1 and H2, respectively. Three weeks before H1, the subjects underwent one control experiment in normoxia (N; inspired oxygen fraction 20.9%) without any treatment. Serum alpha-tocopherol was significantly higher after treatment with antioxidants compared with placebo. Capillary Po(2) declined during H without significant differences between antioxidants and placebo. Plasma peroxide levels were lower under antioxidant treatment but not affected by hypoxia. The response of Epo to H did not show significant differences between antioxidant [maximum increase (means, 95% confidence interval): +121%, +66 to +176%] and placebo conditions (+108%, +68 to +149%). Similarly, hypoxia-induced increase of Epo corrected for diurnal variations, as revealed during N, did not differ between antioxidants and placebo. Individual variability of Epo in response to H was not related to the individual degree of hypoxemia during H. Our results do not support the assumption that ROS play a major modulating role in the response of Epo to short-term normobaric hypoxia in humans.
近期研究表明，活性氧（ROS）参与了缺氧时启动的细胞内信号传导过程。我们研究了ROS在人体血浆促红细胞生成素（Epo）对短期常压缺氧反应中的作用。12名男性受试者两次暴露于4小时的常压缺氧环境（H；吸入氧分数为12.5%），两次实验之间间隔6周（H1和H2）。采用随机安慰剂对照交叉设计，受试者在H1和H2之前分别口服抗氧化剂全反式α-生育酚（800毫克/天，共3周）和α-硫辛酸（600毫克/天，共2周）的组合或安慰剂。在H1前3周，受试者在常氧环境（N；吸入氧分数为20.9%）下进行一次无任何治疗的对照实验。与安慰剂相比，抗氧化剂治疗后血清α-生育酚显著升高。在缺氧期间毛细血管血氧分压下降，抗氧化剂组和安慰剂组之间无显著差异。抗氧化剂治疗下血浆过氧化物水平较低，但不受缺氧影响。Epo对缺氧的反应在抗氧化剂组[最大增加量（均值，95%置信区间）：+121%，+66%至+176%]和安慰剂组（+108%，+68%至+149%）之间无显著差异。同样，如在常氧期间所显示的，经日变化校正后的缺氧诱导的Epo增加在抗氧化剂组和安慰剂组之间也无差异。Epo对缺氧反应的个体变异性与缺氧期间个体低氧血症程度无关。我们的结果不支持ROS在人体Epo对短期常压缺氧反应中起主要调节作用这一假设。
