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新型自由基清除剂 4'-羟基-2-取代苯基硝酮氮氧自由基在急性高原缺氧小鼠中的抗氧化作用。

The antioxidative effect of a novel free radical scavenger 4'-hydroxyl-2-substituted phenylnitronyl nitroxide in acute high-altitude hypoxia mice.

机构信息

Department of Pharmacy, General Hospital of Lanzhou Command of PLA, Lanzhou, China.

出版信息

Biol Pharm Bull. 2013;36(6):917-24. doi: 10.1248/bpb.b12-00854. Epub 2013 Mar 12.

DOI:10.1248/bpb.b12-00854
PMID:23486089
Abstract

Acute mountain sickness is caused by sub-acute hypoxia in healthy individuals going rapidly to altitude. Both tissue hypoxia in vitro and whole-body hypoxia in vivo have been found to promote the release of reactive oxygen species. Nitronyl nitroxide can trap free radicals such as ·NO or ·OH, and may therefore be efficient protective agents. This study assessed the ability of nitronyl nitroxide to against acute mountain sickness as a free radical scavenger in acute high-altitude hypoxia mice model. Normobaric hypoxia and hypobaric hypoxia model were used to estimate the protect effects of nitronyl nitroxide against acute mountain sickness. Low pressure oxygen compartment system was used to stimulate high-altitude hypobaric hypoxia environment. Mice in nitronyl nitroxide groups survived longer than acetazolamide group in normobaric hypoxia test. Hydrogen peroxide (H2O2) and malondialdehyde (MDA) increased in both cerebrum and myocardium in vehicle group. The results indicated more radicals were generated during high-altitude hypobaric hypoxia environment. In therapeutic groups H2O2 and MDA were significantly reduced while the activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) were similar to normal group. These results demonstrated that nitronyl nitroxide was an efficient tissue radical scavenger and a potential protective agent for acute mountain sickness.

摘要

急性高原病是健康个体迅速进入高原时发生的亚急性缺氧引起的。体外组织缺氧和体内全身缺氧都被发现可促进活性氧的释放。硝酰氮氧化物可以捕获自由基,如·NO 或·OH,因此可能是有效的保护剂。本研究评估了硝酰氮氧化物作为自由基清除剂在急性高原缺氧小鼠模型中对急性高原病的防治作用。常压缺氧和低压缺氧模型用于评估硝酰氮氧化物对急性高原病的保护作用。低压氧舱系统用于模拟高原低压缺氧环境。在常压缺氧试验中,硝酰氮氧化物组的小鼠比乙酰唑胺组存活时间更长。在对照组中,大脑和心肌中的过氧化氢(H2O2)和丙二醛(MDA)含量增加。结果表明,在高原低压缺氧环境中产生了更多的自由基。在治疗组中,H2O2 和 MDA 显著降低,而超氧化物歧化酶(SOD)、谷胱甘肽过氧化物酶(GSH-Px)和过氧化氢酶(CAT)的活性与正常组相似。这些结果表明,硝酰氮氧化物是一种有效的组织自由基清除剂,也是急性高原病的潜在保护剂。

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