Freudenthaler S M, Schreeb K-H, Wiese A, Pilz J, Gleiter C H
Department of Clinical Pharmacology, University of Tuebingen, Germany.
Acta Physiol Scand. 2002 Mar;174(3):231-5. doi: 10.1046/j.1365-201x.2002.00946.x.
The present study was carried out to evaluate a model of a hypoxic stimulus of erythropoietin (EPO) production in humans and to investigate the role of free oxygen radicals in human EPO production. The study was conducted as an open, randomized, parallel, placebo-controlled trial. Thirty-six healthy male volunteers received a hypoxic treatment (13% O(2)) with a respiration mask for 6 h. During the period of hypoxia, the volunteers received as a short-term treatment either 1200 mg thioctic acid, or N-acetylcysteine 600 mg or placebo (0.9% sodium chloride). The EPO concentration in plasma increased up to 290% of the baseline level in all three groups. No statistically significant differences of AUC(EPO(0-48 h)) could be demonstrated between the groups. The malondialdehyde (MDA) concentration in plasma increased significantly (P < 0.001) 2 h after termination of hypoxia (mean 129.8 +/- 6.8% of the baseline) in all three groups.
Taken together, our in-vivo results do not support a gross modulatory effect of a short-term treatment with radical scavenging agents on EPO-production during or after hypoxia in humans, as derived from the detected changes of MDA-concentrations in peripheral plasma.
本研究旨在评估人类促红细胞生成素（EPO）产生的低氧刺激模型，并研究游离氧自由基在人类EPO产生中的作用。该研究作为一项开放、随机、平行、安慰剂对照试验进行。36名健康男性志愿者使用呼吸面罩接受6小时的低氧治疗（13%氧气）。在低氧期间，志愿者接受短期治疗，分别为1200毫克硫辛酸、600毫克N-乙酰半胱氨酸或安慰剂（0.9%氯化钠）。所有三组血浆中EPO浓度均升高至基线水平的290%。各组之间未显示出AUC（EPO（0 - 48小时））有统计学显著差异。所有三组在低氧结束后2小时血浆中丙二醛（MDA）浓度显著升高（P < 0.001）（平均为基线的129.8 +/- 6.8%）。
综合来看，我们的体内研究结果不支持自由基清除剂短期治疗对人类低氧期间或之后EPO产生有显著调节作用，这是根据外周血浆中MDA浓度的检测变化得出的。
