水杨酸可阻断消炎痛和阿司匹林对大鼠胃黏膜中环氧化酶的抑制作用。

Salicylic acid blocks indomethacin- and aspirin-induced cyclo-oxygenase inhibition in rat gastric mucosa.

作者信息

Ligumsky M, Hansen D G, Kauffman G L

出版信息

Gastroenterology. 1982 Nov;83(5):1043-6.

Abstract

Salicylic acid reduces gastric mucosal lesions induced by aspirin and indomethacin. Aspirin and indomethacin reduce gastric mucosal cyclo-oxygenase activity. These studies were designed to determine whether or not salicylic acid interacts with gastric mucosal cyclo-oxygenase, decreasing the inhibitory effect of aspirin and indomethacin as has been observed in platelets and vascular tissue. The interaction between salicylic acid and two cyclo-oxygenase inhibitors, indomethacin and aspirin, was assessed on ex vivo prostaglandin generation in the rat gastric mucosa. Salicylic acid (100 mg/kg) was administered orally 30 min before the subcutaneous injection of either indomethacin (0.5-10 mg/kg) or aspirin (5.0-20 mg/kg). Pretreatment produced a shift of the mean 50% inhibitory dose for PGF2 alpha formation from 0.92 to 7.6 mg/kg for indomethacin and from 7.8 to 20 mg/kg for aspirin. Similar results were achieved with ex vivo prostacyclin synthesis as measured by the level of 6-keto-PGF 1 alpha. These data are consistent with competitive enzyme kinetics, and may, in part, explain the protective effect of salicylic acid against the ulcerogenicity of aspirin and indomethacin on the gastric mucosa.

摘要

水杨酸可减轻阿司匹林和吲哚美辛所致的胃黏膜损伤。阿司匹林和吲哚美辛可降低胃黏膜环氧化酶活性。这些研究旨在确定水杨酸是否与胃黏膜环氧化酶相互作用，如同在血小板和血管组织中所观察到的那样，降低阿司匹林和吲哚美辛的抑制作用。在大鼠胃黏膜中，通过体外前列腺素生成评估了水杨酸与两种环氧化酶抑制剂（吲哚美辛和阿司匹林）之间的相互作用。在皮下注射吲哚美辛（0.5 - 10 mg/kg）或阿司匹林（5.0 - 20 mg/kg）前30分钟，口服给予水杨酸（100 mg/kg）。预处理使吲哚美辛导致PGF2α生成的平均50%抑制剂量从0.92 mg/kg变为7.6 mg/kg，使阿司匹林导致PGF2α生成的平均50%抑制剂量从7.8 mg/kg变为20 mg/kg。通过6 - 酮 - PGF1α水平测定的体外前列环素合成也得到了类似结果。这些数据与竞争性酶动力学一致，并且可能部分解释了水杨酸对阿司匹林和吲哚美辛所致胃黏膜溃疡形成的保护作用。