Bjorkman D J
Division of Gastroenterology, University of Utah School of Medicine, Salt Lake City 84132, USA.
Am J Med. 1998 Jul 27;105(1B):8S-12S. doi: 10.1016/s0002-9343(98)00069-2.
Cyclic prostanoids play important physiologic roles in inflammation and maintaining normal function of several organ systems. Prostaglandin production requires the conversion of arachidonate to the intermediate prostaglandin H2, by the 2-step cyclo-oxygenation and peroxidation catalyzed by the enzyme cyclo-oxygenase (also called prostaglandin H synthase). Aspirin and nonsteroidal anti-inflammatory drugs (NSAIDs) block the production of cyclic prostanoids by binding in different ways to this enzyme and blocking the active site. This results in decreased inflammation, but it can also produce side effects in the gastrointestinal tract, kidney, and platelets. Recent data demonstrate that there are 2 isoforms of the cyclo-oxygenase enzyme, called COX-1 and COX-2. These isoforms are similar in size, substrate specificity, and kinetics, but vary in their expression and distribution. Normal physiologic functions appear to be maintained by COX-1, while COX-2 appears to mediate the inflammatory response. Nonsteroidal drugs with selective inhibitory activity on the COX-2 isoform should theoretically decrease inflammation while maintaining normal physiologic prostaglandin levels. Current NSAIDs are not selective enough to confirm this, but newer, more selective inhibitors of COX-2 may answer this important question.
环前列腺素在炎症以及维持多个器官系统的正常功能中发挥着重要的生理作用。前列腺素的产生需要通过环氧化酶（也称为前列腺素H合酶）催化的两步环氧化和过氧化反应，将花生四烯酸转化为中间产物前列腺素H2。阿司匹林和非甾体抗炎药（NSAIDs）通过以不同方式与该酶结合并阻断其活性位点，从而阻断环前列腺素的产生。这会导致炎症减轻，但也可能在胃肠道、肾脏和血小板中产生副作用。最近的数据表明，环氧化酶有两种同工型，称为COX-1和COX-2。这些同工型在大小、底物特异性和动力学方面相似，但在表达和分布上有所不同。正常生理功能似乎由COX-1维持，而COX-2似乎介导炎症反应。理论上，对COX-2同工型具有选择性抑制活性的非甾体药物应能在维持正常生理前列腺素水平的同时减轻炎症。目前的NSAIDs选择性不够强，无法证实这一点，但更新的、对COX-2更具选择性的抑制剂可能会回答这个重要问题。
