THE MECHANISMS OF ACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS
THE MECHANISMS OF ACTION OF NONSTEROIDAL ANTIINFLAMMATORY DRUGS
复制标题
DOI：
10.1002/anr.1780320102
复制
发表时间：
1989-01-01
影响因子：
--
通讯作者：
WEISSMANN, G
中科院分区：
文献类型：
--
作者：
ABRAMSON, SB;WEISSMANN, G
在哺乳动物物种和最古老的多细胞动物中，NSAID 抑制细胞活化，显然对 PG 生物合成没有影响。因此，可以提出另一种假设来解释这些药物的抗炎作用。显然，低剂量的阿司匹林和大多数新型 NSAID 会抑制花生四烯酸中 PG 的生物合成，而稳定的 PG 已被证明可以介导发热、痛觉过敏、血管舒张（水肿）和多种白细胞介素 1 依赖性反应。然而，在高剂量下，阿司匹林、水杨酸钠和新型 NSAID（抗炎剂量）会抑制非 PG 依赖性过程，例如各种酶的活性、软骨细胞的蛋白聚糖合成、跨膜离子流和趋化剂结合。这些效应很可能是由于阿司匹林类药物能够插入质膜的脂质双层，从而破坏正常的信号传导事件和蛋白质-蛋白质相互作用。 NSAID 抑制炎症细胞（如中性粒细胞）活化的能力可能有助于此类药物的抗炎特性。
In mammalian species and in the oldest of multicellular animal forms, NSAIDs inhibit cell activation, apparently in the absence of effects on PG biosynthesis. Thus, an alternative hypothesis can be proposed to account for the antiinflammatory effects of these drugs. Clearly, at low doses aspirin and most of the newer NSAIDs inhibit the biosynthesis of PGs from arachidonic acid, and stable PGs have been shown to mediate fever, hyperalgesia, vasodilation (edema), and several interleukin-1-dependent responses. At high doses, however, aspirin, sodium salicylate, and the newer NSAIDs (at antiinflammatory doses) inhibit non-PG-dependent processes, such as the activity of a variety of enzymes, proteoglycan synthesis by chondrocytes, transmembrane ion fluxes, and chemoattractant binding. These effects are most likely due to the capacity of aspirin-like drugs to insert into the lipid bilayer of plasma membranes, where they disrupt normal signaling events and protein-protein interactions. The ability of NSAIDs to thereby inhibit the activation of inflammatory cells such as the neutrophil may contribute to the antiinflammatory properties of this class of drugs.