Fan Peng-Cheng, Ma Hui-Ping, Jiang Wei, Li Lin, Ren Jun, Jing Lin-lin, Jia Zheng-Ping
Department of Pharmacy, General Hospital of Lanzhou Command of PLA.
Biol Pharm Bull. 2015;38(9):1280-9. doi: 10.1248/bpb.b15-00131.
Nitric oxide (NO) may act as either a pro-oxidant or an antioxidant in biological systems. Previous work has found inhalation of NO improved survival in a high altitude rat model. NO donor isosorbide mononitrate derivants might have a protective effect against hypoxia. We synthesized a series of isosorbide mononitrate derivant compounds to test their anti-hypoxia activities. Normobaric hypoxia and hypobaric hypoxia models were used to study the protective role of NO donor in mice. The results showed isosorbide mononitrate derivants had protective effects in hypoxia mice. Among those compounds, acetyl ferulic isosorbide mononitrate (AFIM) was the most effective. It prolonged the survival time during the normobaric hypoxia test. It decreased malondialdehyde (MDA) and H2O2 in hypobaric hypoxia mice. The antioxidase activities of superoxide dismutase (SOD), glutathione peroxidase (GSH-Px) and catalase (CAT) remained in normal ranges in the AFIM group. As a sign of mitochondrial dysfunction, the activities of ATPase were down regulated in mice under hypobaric hypoxia conditions. AFIM also protected ATPase activities. The protective effects of AFIM might come from a sustained NO supply and the release of acetyl ferulic acid with anti-oxidant activity.
一氧化氮（NO）在生物系统中既可能作为促氧化剂，也可能作为抗氧化剂。先前的研究发现，吸入NO可提高高原大鼠模型的存活率。NO供体单硝酸异山梨酯衍生物可能对缺氧具有保护作用。我们合成了一系列单硝酸异山梨酯衍生物化合物，以测试它们的抗缺氧活性。采用常压缺氧和低压缺氧模型研究NO供体对小鼠的保护作用。结果表明，单硝酸异山梨酯衍生物对缺氧小鼠具有保护作用。在这些化合物中，乙酰阿魏酸单硝酸异山梨酯（AFIM）最为有效。它延长了常压缺氧试验中的存活时间。它降低了低压缺氧小鼠体内的丙二醛（MDA）和过氧化氢（H2O2）水平。在AFIM组中，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）的抗氧化酶活性保持在正常范围内。作为线粒体功能障碍的一个标志，在低压缺氧条件下，小鼠体内ATP酶的活性被下调。AFIM也保护了ATP酶的活性。AFIM的保护作用可能来自持续的NO供应以及具有抗氧化活性的乙酰阿魏酸的释放。
