Hirasawa N, Ohuchi K, Watanabe M, Tsurufuji S
Department of Biochemistry, Faculty of Pharmaceutical Sciences, Tohoku University, Miyagi, Japan.
Eur J Pharmacol. 1987 Dec 15;144(3):267-75. doi: 10.1016/0014-2999(87)90379-7.
The mechanism of the inhibitory action of cyclooxygenase inhibitors on leukocyte accumulation in the inflammatory locus was investigated in an allergic inflammation of the air pouch types in rats. Three kinds of cyclooxygenase inhibitors, indomethacin, diclofenac and tiaprofenic acid, caused not only inhibition of the vascular permeability response and leukocyte accumulation but also elevation of histamine levels in the exudate. These effects of indomethacin were all reversed by local administration of prostaglandin E2. Pyrilamine, an H1 antagonist, did not affect the anti-inflammatory actions of indomethacin. The H2 antagonists, cimetidine, ranitidine and famotidine, decreased the inhibitory effect of indomethacin on leukocyte accumulation without affecting the inhibitory action on vascular permeability. These results indicate that the inhibitory action of cyclooxygenase inhibitors on leukocyte accumulation is derived from their blocking effect against generation of PGE2 which works as an inhibitory factor on the production of histamine in the inflammatory tissues.
在大鼠气囊型过敏性炎症中，研究了环氧化酶抑制剂对炎症部位白细胞聚集的抑制作用机制。三种环氧化酶抑制剂，吲哚美辛、双氯芬酸和噻洛芬酸，不仅抑制血管通透性反应和白细胞聚集，还使渗出液中组胺水平升高。吲哚美辛的这些作用均可被局部给予前列腺素E2逆转。H1拮抗剂吡苄明不影响吲哚美辛的抗炎作用。H2拮抗剂西咪替丁、雷尼替丁和法莫替丁降低了吲哚美辛对白细胞聚集的抑制作用，而不影响其对血管通透性的抑制作用。这些结果表明，环氧化酶抑制剂对白细胞聚集的抑制作用源于其对PGE2生成的阻断作用，PGE2在炎症组织中作为组胺产生的抑制因子发挥作用。
