Anti-hypoxia Activity of the Novel NO Donor Acetyl Ferulic Isosorbide Mononitrate in Acute High-Altitude Hypoxia Mice
Anti-hypoxia Activity of the Novel NO Donor Acetyl Ferulic Isosorbide Mononitrate in Acute High-Altitude Hypoxia Mice
复制标题
新型 NO 供体乙酰阿魏酸单硝酸异山梨酯对急性高原缺氧小鼠的抗缺氧活性。
DOI：
10.1248/bpb.b15-00131
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发表时间：
2015-09-01
影响因子：
2
通讯作者：
Jia, Zheng-Ping
中科院分区：
文献类型：
--
作者：
Fan, Peng-Cheng;Ma, Hui-Ping;Jia, Zheng-Ping
一氧化氮（NO）在生物系统中既可以作为促氧化剂，也可以作为抗氧化剂。先前的工作已经发现吸入NO改善了高海拔大鼠模型的存活率。NO供体单硝酸异山梨酯衍生物可能具有抗缺氧作用。本文合成了一系列单硝酸异山梨酯衍生物，并对其进行了抗缺氧活性测试。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（AACEI）是最有效的。延长常压缺氧实验小鼠的存活时间。降低低压缺氧小鼠的丙二醛（MDA）和H_2O_2。黄芪组超氧化物歧化酶（SOD）、谷胱甘肽过氧化物酶（GSH-Px）和过氧化氢酶（CAT）的抗氧化酶活性在正常范围内。作为线粒体功能障碍的标志，ATP酶活性在低压缺氧条件下的小鼠中下调。黄芪还保护ATP酶活性。黄芪的保护作用可能来自于持续的NO供应和具有抗氧化活性的乙酰阿魏酸的释放。
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.