内源性尿酸生成可增强暴露于高海拔地区的健康低地受试者的血浆抗氧化能力。

Endogenous urate production augments plasma antioxidant capacity in healthy lowland subjects exposed to high altitude.

作者信息

Baillie J Kenneth, Bates Matthew G D, Thompson A A Roger, Waring W Stephen, Partridge Roland W, Schnopp Martin F, Simpson Alistair, Gulliver-Sloan Fiona, Maxwell Simon R J, Webb David J

机构信息

Apex (Altitude Physiology Expeditions), c/o College of Medicine & Veterinary Medicine, University of Edinburgh, The Queen's Medical Research Institute, 47 Little France Crescent, Edinburgh, UK.

出版信息

Chest. 2007 May;131(5):1473-8. doi: 10.1378/chest.06-2235.

DOI:10.1378/chest.06-2235

PMID:17494796

Abstract

BACKGROUND

Both tissue hypoxia in vitro, and whole-body hypoxia in vivo, have been found to promote the release of reactive oxygen species (ROS) that are potentially damaging to the cardiovascular system. Antioxidant systems protect against oxidative damage by ROS and may exhibit some degree of responsiveness to oxidative stimuli. Production of urate, a potent soluble antioxidant, is increased in hypoxic conditions. We aimed to determine whether urate is an important antioxidant defense in healthy subjects exposed to hypoxia.

METHODS

We conducted a cohort study of 25 healthy lowland volunteers during acute exposure to high altitude (4 days at 3,600 m, followed by 10 days at 5,200 m) on the Apex high-altitude research expedition to Bolivia. We measured markers of oxidative stress (8-isoprostane F2), serum urate concentration, and total plasma antioxidant activity by two techniques: 2,2'-amino-di-[3-ethylbenzthiazole sulfonate] spectrophotometry (total antioxidant status [TAS]) and enhanced chemiluminescence (ECL).

RESULTS

On ascent, F2-isoprostane levels were significantly elevated compared with those at sea level (p < 0.01). After 1 week at high altitude, plasma antioxidant capacity (AOC) by both TAS and ECL, and serum urate concentration were significantly elevated (each p < 0.01 vs sea level), and F2-isoprostane levels were reduced to values at sea level. There was a highly significant correlation between plasma urate and AOC at this stage (ECL, r(2) = 0.59, p = 0.0001; TAS, r(2) = 0.30, p = 0.0062).

CONCLUSIONS

Our results support the hypothesis that urate may act as a responsive endogenous antioxidant in high-altitude hypoxia.

摘要

背景

体外组织缺氧和体内全身缺氧均已被发现可促进活性氧（ROS）的释放，而活性氧可能对心血管系统造成损害。抗氧化系统可保护机体免受ROS的氧化损伤，并可能对氧化刺激表现出一定程度的反应。尿酸是一种强效的可溶性抗氧化剂，在缺氧条件下其生成会增加。我们旨在确定尿酸是否是暴露于缺氧环境中的健康受试者的一种重要抗氧化防御物质。

方法

在前往玻利维亚的阿佩克斯高海拔研究考察中，我们对25名健康的低地志愿者进行了一项队列研究，这些志愿者在急性暴露于高海拔环境（在3600米处停留4天，随后在5200米处停留10天）期间。我们通过两种技术测量氧化应激标志物（8-异前列腺素F2）、血清尿酸浓度和总血浆抗氧化活性：2,2'-氨基二-[3-乙基苯并噻唑磺酸盐]分光光度法（总抗氧化状态[TAS]）和增强化学发光法（ECL）。

结果

与海平面时相比，上升过程中F2-异前列腺素水平显著升高（p < 0.01）。在高海拔停留1周后，通过TAS和ECL测量的血浆抗氧化能力（AOC）以及血清尿酸浓度均显著升高（与海平面相比，各p < 0.01），且F2-异前列腺素水平降至海平面时的值。在此阶段，血浆尿酸与AOC之间存在高度显著的相关性（ECL，r(2) = 0.59，p = 0.0001；TAS，r(2) = 0.30，p = 0.0062）。