Aeberhard E E, Henderson S A, Arabolos N S, Griscavage J M, Castro F E, Barrett C T, Ignarro L J
Department of Pediatrics, School of Medicine, University of California, Los Angeles 90024.
Biochem Biophys Res Commun. 1995 Mar 28;208(3):1053-9. doi: 10.1006/bbrc.1995.1441.
Increased nitric oxide production is associated with acute and chronic inflammatory processes. Accordingly, we tested the hypothesis that the therapeutic action of nonsteroidal anti-inflammatory drugs could be attributed at least in part to inhibition of excess nitric oxide production. We report here that sodium salicylate, aspirin, ibuprofen, and indomethacin markedly inhibited the appearance of the inducible inflammatory nitric oxide synthase in rat alveolar macrophages activated with lipopolysaccharide and interferon gamma. We attribute the mechanism of nitric oxide synthase inhibition by nonsteroidal anti-inflammatory drugs to pretranslational control of enzyme expression and not to direct inhibition of enzymatic activity. These observations indicate that the chronic anti-inflammatory action of nonsteroidal anti-inflammatory drugs may be due not only to inhibition of prostaglandin synthesis but also to inhibition of inducible nitric oxide synthase gene expression and nitric oxide synthesis.
一氧化氮生成增加与急慢性炎症过程相关。因此，我们检验了这样一个假说，即非甾体抗炎药的治疗作用至少部分可归因于对过量一氧化氮生成的抑制。我们在此报告，水杨酸钠、阿司匹林、布洛芬和吲哚美辛显著抑制了用脂多糖和γ干扰素激活的大鼠肺泡巨噬细胞中诱导型炎性一氧化氮合酶的出现。我们将非甾体抗炎药抑制一氧化氮合酶的机制归因于酶表达的翻译前控制，而非酶活性的直接抑制。这些观察结果表明，非甾体抗炎药的慢性抗炎作用可能不仅归因于对前列腺素合成的抑制，还归因于对诱导型一氧化氮合酶基因表达和一氧化氮合成的抑制。
