Young J M, Tomolonis A J
Institute of Biological Sciences, Syntex Research, Palo Alto, CA 94304.
Agents Actions. 1987 Aug;21(3-4):314-5. doi: 10.1007/BF01966501.
Indomethacin was administered subcutaneously to rats, 4 mg/kg/day for 4 consecutive days in order to produce erosions of the small intestine which were scored at necropsy on day 5. Orally administered phenidone (up to 250 mg/kg/day), a mixed cycloocygenase-lipoxygenase inhibitor, failed to produce intestinal erosions, but tended to exacerbate indomethacin-induced erosions. A 5-LO inhibitor, diphenyldisulfide, provided significant protection at 10-100 mg/kg when given orally to indomethacin-treated rats. Sulfasalazine, auranofin and cyproheptadine, but not cimetidine, also protected, suggesting a role for mast cell activation and leukotriene generation in indomethacin-induced ulcerogenesis.
给大鼠皮下注射吲哚美辛，剂量为4毫克/千克/天，连续4天，以造成小肠糜烂，于第5天尸检时进行评分。口服给予苯茚二酮（剂量高达250毫克/千克/天），一种环氧化酶 - 脂氧合酶混合抑制剂，未能造成肠道糜烂，但倾向于加重吲哚美辛诱导的糜烂。一种5 - 脂氧合酶抑制剂二苯基二硫化物，在以10 - 100毫克/千克的剂量口服给予吲哚美辛处理的大鼠时，提供了显著的保护作用。柳氮磺胺吡啶、金诺芬和赛庚啶（但不包括西咪替丁）也具有保护作用，提示肥大细胞活化和白三烯生成在吲哚美辛诱导的溃疡形成中起作用。
