Harada Y, Kawamura M, Hatanaka K, Saito M, Ogino M, Ohno T, Ogino K, Yang Q
Department of Pharmacology, Kitasato University School of Medicine, Sagamihara, Japan.
Prostaglandins Other Lipid Mediat. 1998 Apr;55(5-6):345-58. doi: 10.1016/s0090-6980(98)00033-1.
The present study examined the inhibitory profiles of NS-398 and nimesulide against prostaglandin (PG) formation in inflammatory and non-inflammatory sites, and compared them with those of aspirin and indomethacin. In vitro, indomethacin inhibited PGH synthase (PGHS)-1 and PGHS-2 almost equally, while NS-398 and nimesulide inhibited only PGHS-2. NS-398 (1, 10 mg/kg) and nimesulide (3 mg/kg) slowed the rate of plasma exudation and thus the exudate accumulation in rat carrageenin-induced pleurisy. Aspirin (30, 100 mg/kg) and indomethacin (10 mg/kg) also reduced this rate. NS-398 and nimesulide reduced the PGE2 more potently than TXB2 and 6-keto-PGF1 alpha in the exudate. However, aspirin and indomethacin did not exhibit this selectivity. The levels of PGE2 correlated significantly with the plasma exudation rate. Moreover, nimesulide (3 mg/kg) did not affect PGE2 formation in rat stomachs injected with 1 M NaCl solution, while indomethacin (10 mg/kg) reduced it. Thus, NS-398 and nimesulide exhibit different inhibitory profiles from aspirin and indomethacin against PG formation. These results suggest that PGE2 may be produced by PGHS-2 in the inflammatory site, and may play a more prominent role than PGI2 in plasma exudation.
本研究检测了NS - 398和尼美舒利在炎症和非炎症部位对前列腺素（PG）生成的抑制情况，并将它们与阿司匹林和吲哚美辛的抑制情况进行比较。在体外，吲哚美辛对PGH合酶（PGHS）- 1和PGHS - 2的抑制作用几乎相同，而NS - 398和尼美舒利仅抑制PGHS - 2。NS - 398（1、10mg/kg）和尼美舒利（3mg/kg）减缓了大鼠角叉菜胶诱导胸膜炎中血浆渗出率，从而减少了渗出液的积聚。阿司匹林（30、100mg/kg）和吲哚美辛（10mg/kg）也降低了该速率。在渗出液中，NS - 398和尼美舒利对PGE2的降低作用比对TXB2和6 - 酮 - PGF1α更有效。然而，阿司匹林和吲哚美辛没有表现出这种选择性。PGE2的水平与血浆渗出率显著相关。此外，尼美舒利（3mg/kg）对注射1M NaCl溶液的大鼠胃中PGE2的生成没有影响，而吲哚美辛（10mg/kg）则降低了其生成。因此，NS - 398和尼美舒利在PG生成方面表现出与阿司匹林和吲哚美辛不同的抑制情况。这些结果表明，PGE2可能由炎症部位的PGHS - 2产生，并且在血浆渗出中可能比PGI2起更突出的作用。
