Gilroy D W, Tomlinson A, Willoughby D A
Department of Experimental Pathology, William Harvey Research Institute, Saint Bartholomew's and the Royal London School of Medicine and Dentistry, UK.
Eur J Pharmacol. 1998 Aug 21;355(2-3):211-7. doi: 10.1016/s0014-2999(98)00508-1.
The anti-inflammatory activity of drugs more selective for cyclooxgenase isoform inhibition (cyclooxygenase 1, cyclooxygenase 2), were compared in rat carrageenin-induced pleurisy. Suppression of inflammation by cyclooxygenase 2-selective inhibitors, NS-398 (N-[-2-cyclohexyloxy]-4-nitrophenyl methanesulphonamide) and nimesulide (4-nitro-2-phenoxy-methanesulfonanilide), and by piroxicam and aspirin, more selective for cyclooxygenase 1, was measured. Piroxicam and aspirin significantly inhibited inflammatory cell influx, exudate and prostaglandin E2 formation, 6 h after carrageenin injection. Cyclooxygenase 2 inhibitors had little effect on these parameters with NS-398 alone reducing prostaglandin E2 levels, but increasing levels of leukotriene B4. In contrast, at 3 h after carrageenin injection, cyclooxygenase 2 inhibitors significantly inhibited all inflammatory parameters however suppression with piroxicam and aspirin was greater, and more pronounced than at 6 h. NS-398 and nimesulide dosing did not reduce thromboxane B2 production from platelets isolated from rats with carrageenin-induced pleurisy, demonstrating that at the doses used, cyclooxygenase 2 inhibitors did not inhibit cyclooxygenase 1, as platelets contain only this isoform. Therefore, in the rat carrageenin-induced pleurisy, drugs more selective for the inhibition of cyclooxygenase 1 attenuate inflammation over a wider time frame than cyclooxygenase 2-selective drugs, suggesting a significant role for cyclooxygenase 1 in this model. Inhibition of cyclooxygenase 2 by NS-398 however, resulted in an increase in the potent chemoattractant leukotriene B4.
在大鼠角叉菜胶诱导的胸膜炎中，比较了对环氧化酶同工酶抑制作用更具选择性的药物（环氧化酶1、环氧化酶2）的抗炎活性。测定了环氧化酶2选择性抑制剂NS-398（N-[-2-环己氧基]-4-硝基苯基甲磺酰胺）和尼美舒利（4-硝基-2-苯氧基-甲磺酰苯胺）以及对环氧化酶1更具选择性的吡罗昔康和阿司匹林对炎症的抑制作用。角叉菜胶注射6小时后，吡罗昔康和阿司匹林显著抑制炎症细胞浸润、渗出物和前列腺素E2的形成。环氧化酶2抑制剂对这些参数几乎没有影响，单独使用NS-398仅降低前列腺素E2水平，但增加白三烯B4水平。相比之下，在角叉菜胶注射3小时后，环氧化酶2抑制剂显著抑制所有炎症参数，然而吡罗昔康和阿司匹林的抑制作用更大，且比6小时时更明显。NS-398和尼美舒利给药并未降低从角叉菜胶诱导胸膜炎的大鼠分离的血小板中血栓素B2的产生，表明在所使用的剂量下，环氧化酶2抑制剂并未抑制环氧化酶1，因为血小板仅含有这种同工酶。因此，在大鼠角叉菜胶诱导的胸膜炎中，对环氧化酶1抑制作用更具选择性的药物比环氧化酶2选择性药物在更宽的时间范围内减轻炎症，这表明环氧化酶1在该模型中起重要作用。然而，NS-398对环氧化酶2的抑制导致强效趋化因子白三烯B4增加。
