Vane J R, Botting R M
The William Harvey Research Institute, St. Bartholomew's and the Royal London School of Medicine and Dentistry, Queen Mary and Westfield College, UK.
Inflamm Res. 1998 Oct;47 Suppl 2:S78-87. doi: 10.1007/s000110050284.
Nonsteroidal anti-inflammatory drugs (NSAIDs) produce their therapeutic activities through inhibition of cyclooxygenase (COX), the enzyme that makes prostaglandins (PGs). They share, to a greater or lesser degree, the same side effects, including gastric and renal toxicity. Recent research has shown that there are at least two COX isoenzymes. COX-1 is constitutive and makes PGs that protect the stomach and kidney from damage. COX-2 is induced by inflammatory stimuli, such as cytokines, and produces PGs that contribute to the pain and swelling of inflammation. Thus, selective COX-2 inhibitors should be anti-inflammatory without side effects on the kidney and stomach. Of course, selective COX-2 inhibitors may have other side effects and perhaps other therapeutic potential. For instance, COX-2 (and not COX-1) is thought to be involved in ovulation and in labor. In addition, the well-known protective action of aspirin on colon cancer may be through an action on COX-2, which is expressed in this disease. Moreover, NSAIDs delay the progress of Alzheimer's disease. Thus, selective COX-2 inhibitors may demonstrate new important therapeutic benefits as anticancer agents, as well as in preventing premature labor and perhaps even retarding the progression of Alzheimer's disease.
非甾体抗炎药（NSAIDs）通过抑制环氧化酶（COX）发挥其治疗作用，COX是一种能生成前列腺素（PGs）的酶。它们或多或少都有相同的副作用，包括胃毒性和肾毒性。最近的研究表明，至少存在两种COX同工酶。COX-1是组成型的，生成的PGs可保护胃和肾脏免受损伤。COX-2由炎症刺激因子如细胞因子诱导产生，其生成的PGs会导致炎症疼痛和肿胀。因此，选择性COX-2抑制剂应具有抗炎作用，且对肾脏和胃无副作用。当然，选择性COX-2抑制剂可能有其他副作用，或许也有其他治疗潜力。例如，COX-2（而非COX-1）被认为与排卵和分娩有关。此外，阿司匹林对结肠癌的著名保护作用可能是通过作用于COX-2实现的，COX-2在这种疾病中表达。而且，NSAIDs可延缓阿尔茨海默病的进展。因此，选择性COX-2抑制剂作为抗癌药物，以及在预防早产甚至可能延缓阿尔茨海默病进展方面，可能会展现出新的重要治疗益处。
