Katori M, Majima M, Harada Y
Department of Pharmacology, Kitasato University School of Medicine, Kanagawa, Japan.
Inflamm Res. 1998 Oct;47 Suppl 2:S107-11. doi: 10.1007/s000110050293.
Cyclooxygenase (COX)-2 was induced in an acute exudative inflammatory model (rat carrageenin-induced pleurisy) in which prostaglandin E2, 6-keto-prostaglandin F1alpha, and thromboxane B2 were generated in the pleural fluid. Selective COX-2 inhibitors, such as NS-398, inhibited the plasma exudation and generation of prostaglandin E2, but not that of thromboxane B2 and 6-keto-prostaglandin F1alpha, in the pleural fluid. In proliferative inflammatory models, COX-2 was induced, and selective COX-2 inhibitors suppressed granuloma formation, particularly, microvessel formation. COX-2 was induced during angiogenesis in a sponge model implanted into skin of rat, and the COX-2 inhibitor suppressed the angiogenesis. As induction of COX-2 was reported in osteoblasts, COX-2 was involved in most characteristic responses of acute exudative inflammation, granuloma formation, bone resorption, and pain in rheumatoid arthritis. The prevention of these COX-2 responses provides a rationale for the effectiveness of COX-2 inhibitors in the treatment of rheumatoid arthritis.
在急性渗出性炎症模型（大鼠角叉菜胶诱导的胸膜炎）中可诱导环氧化酶（COX）-2，在此模型中，胸膜液中会生成前列腺素E2、6-酮-前列腺素F1α和血栓素B2。选择性COX-2抑制剂，如NS-398，可抑制血浆渗出和胸膜液中前列腺素E2的生成，但不抑制血栓素B2和6-酮-前列腺素F1α的生成。在增殖性炎症模型中，COX-2被诱导，选择性COX-2抑制剂可抑制肉芽肿形成，尤其是微血管形成。在植入大鼠皮肤的海绵模型中，血管生成过程中会诱导COX-2，COX-2抑制剂可抑制血管生成。由于成骨细胞中也有COX-2诱导的报道，COX-2参与了急性渗出性炎症、肉芽肿形成、骨吸收以及类风湿性关节炎疼痛等最典型的反应。对这些COX-2反应的预防为COX-2抑制剂治疗类风湿性关节炎的有效性提供了理论依据。
