非甾体抗炎药：它们是如何起作用的？

Non-steroidal anti-inflammatory drugs: how do they work?

作者信息

Weissmann G, Korchak H, Ludewig R, Edelson H, Haines K, Levin R I, Herman R, Rider L, Kimmel S, Abramson S

出版信息

Eur J Rheumatol Inflamm. 1987;8(1):6-17.

Abstract

Current dogma holds that non-steroidal anti-inflammatory drugs (NSAIDs) act by inhibition of the synthesis and release of prostaglandins. However, NSAIDs also inhibit the activation of neutrophils, which provoke inflammation by releasing products other than prostaglandins. We now report that NSAIDs (for example, indomethacin, piroxicam) inhibit activation of neutrophils by inflammatory stimuli such as C5-derived peptides and leukotriene B4 even when cyclooxygenase products generated in suspensions of stimulated neutrophils (prostaglandin E and thromboxanes) are present. Sodium salicylate (3mM) greatly inhibited aggregation of neutrophils but had no effect on aggregation of platelets or production of thromboxane induced by arachidonate. Sodium salicylate and other NSAIDs also inhibit calcium movements (45Ca uptake, changes in fluorescence of chlortetracycline and Quin-2). Aspirin, sodium salicylate, indomethacin, and piroxicam also enhanced the post-stimulation rise in intracellular cyclic AMP. NSAIDs therefore inhibit early steps in neutrophil enhance intracellular levels of cyclic AMP.

摘要

目前的理论认为，非甾体抗炎药（NSAIDs）通过抑制前列腺素的合成和释放起作用。然而，NSAIDs也抑制中性粒细胞的活化，而中性粒细胞会通过释放除前列腺素之外的其他产物引发炎症。我们现在报告，即使在受到刺激的中性粒细胞悬液中产生的环氧化酶产物（前列腺素E和血栓烷）存在的情况下，NSAIDs（如吲哚美辛、吡罗昔康）也能抑制诸如C5衍生肽和白三烯B4等炎症刺激物对中性粒细胞的活化。水杨酸钠（3mM）能极大地抑制中性粒细胞的聚集，但对血小板聚集或花生四烯酸诱导的血栓烷生成没有影响。水杨酸钠和其他NSAIDs也抑制钙的移动（45Ca摄取、金霉素和喹啉-2荧光的变化）。阿司匹林、水杨酸钠、吲哚美辛和吡罗昔康还能增强刺激后细胞内环状AMP的升高。因此，NSAIDs抑制中性粒细胞早期的步骤，提高细胞内环状AMP的水平。