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阿司匹林类药物的作用机制。

Mechanism of action of aspirin-like drugs.

作者信息

Vane J R, Botting R M

机构信息

William Harvey Research Institute, St Bartholomew's, London, UK.

出版信息

Semin Arthritis Rheum. 1997 Jun;26(6 Suppl 1):2-10. doi: 10.1016/s0049-0172(97)80046-7.

Abstract

Nonsteroid antiinflammatory drugs (NSAIDs) or aspirin-like drugs act by inhibiting the activity of the cyclooxygenase (COX) enzyme. Two isoforms of COX exist, COX-1, which is constitutively expressed, and COX-2, which is an inducible isoform. Prostaglandins synthesized by the constitutively expressed COX-1 are implicated in the maintenance of normal physiological function and have a 'cytoprotective' action in the stomach. COX-2 expression is normally low but is induced by inflammatory stimuli and cytokines. It is thought that the antiinflammatory actions of NSAIDs are caused by the inhibition of COX-2, whereas the unwanted side effects, such as gastrointestinal and renal toxicity, are caused by the inhibition of the constitutively expressed COX-1. Individual NSAIDs show different selectivities against the COX-1 and COX-2 isoforms. NSAIDs that are selective towards COX-2, such as meloxicam, may have an improved side-effect profile over current NSAIDs. In addition to their use as antiinflammatory agents in the treatment of rheumatoid arthritis and osteoarthritis, selective COX-2 inhibitors may also be beneficial in inhibiting colorectal tumor cell growth and in delaying premature labor.

摘要

非甾体抗炎药(NSAIDs)或类阿司匹林药物通过抑制环氧化酶(COX)的活性发挥作用。COX存在两种同工型,即组成性表达的COX-1和诱导性同工型COX-2。由组成性表达的COX-1合成的前列腺素参与维持正常生理功能,并在胃中具有“细胞保护”作用。COX-2的表达通常较低,但可由炎症刺激和细胞因子诱导。据认为,NSAIDs的抗炎作用是由对COX-2的抑制引起的,而诸如胃肠道和肾脏毒性等不良副作用则是由对组成性表达的COX-1的抑制所致。不同的NSAIDs对COX-1和COX-2同工型表现出不同的选择性。对COX-2有选择性的NSAIDs,如美洛昔康,可能比目前的NSAIDs具有更好的副作用谱。除了作为抗炎剂用于治疗类风湿性关节炎和骨关节炎外,选择性COX-2抑制剂在抑制结肠直肠肿瘤细胞生长和延迟早产方面也可能有益。

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