Seibert K, Zhang Y, Leahy K, Hauser S, Masferrer J, Isakson P
G.D. Searle, Monsanto Company, St. Louis, Missouri 63167, USA.
Adv Exp Med Biol. 1997;400A:167-70. doi: 10.1007/978-1-4615-5325-0_24.
Non-steroidal anti-inflammatory drugs (NSAIDs) are widely used in the treatment of a number of inflammatory diseases and are believed to act via inhibition of the enzyme cyclooxygenase (COX). This enzyme catalyzes the conversion of arachidonic acid to the prostaglandins (PGs). Although commercially available NSAIDs are efficacious anti-inflammatory agents, significant side effects limit their use. Recently two forms of COX were identified-a constitutively expressed COX-1 and a cytokine-inducible COX-2. Potent anti-inflammatory agents like the glucocorticoids are known to inhibit specifically the expression of COX-2 while commercially available NSAIDs like indomethacin inhibit both COX-1 and COX-2. These findings have led to the hypothesis that toxicities associated with NSAID therapy are due to inhibition of the non-regulated or constitutive form of COX (COX-1), whereas therapeutic benefit derives from inhibition of the inducible enzyme, COX-2. We have examined the relative distribution of COX-1 and COX-2 in both normal and inflamed tissues and report that COX-1 expression dominates normal tissues while COX-2 mRNA is induced at the inflammatory site. Furthermore, compounds that selectively inhibit COX-2 are anti-inflammatory without gastric toxicity.
非甾体抗炎药（NSAIDs）广泛用于多种炎症性疾病的治疗，据信其作用机制是抑制环氧化酶（COX）。该酶催化花生四烯酸转化为前列腺素（PGs）。尽管市售的NSAIDs是有效的抗炎药，但显著的副作用限制了它们的使用。最近发现了两种形式的COX——一种组成性表达的COX-1和一种细胞因子诱导的COX-2。已知强效抗炎药如糖皮质激素可特异性抑制COX-2的表达，而市售的NSAIDs如吲哚美辛则抑制COX-1和COX-2。这些发现导致了一种假说，即与NSAID治疗相关的毒性是由于抑制了非调节性或组成性形式的COX（COX-1），而治疗益处则来自于对诱导性酶COX-2的抑制。我们研究了COX-1和COX-2在正常组织和炎症组织中的相对分布，并报告COX-1表达在正常组织中占主导，而COX-2 mRNA在炎症部位被诱导。此外，选择性抑制COX-2的化合物具有抗炎作用且无胃毒性。
