Matsumoto T, Iida M, Nakamura S, Hizawa K, Kuroki F, Fujishima M
Second Department of Internal Medicine, Faculty of Medicine, Kyushu University, Fukuoka, Japan.
Dig Dis Sci. 1994 Apr;39(4):787-95. doi: 10.1007/BF02087425.
The mechanism of nonsteroidal antiinflammatory drug-induced intestinal ulcers is not clearly understood. To evaluate whether immunosuppressants have a preventive effect against indomethacin-induced gastrointestinal damage, we investigated the effects of prednisolone, cyclosporin, and the newly developed immunosuppressant FK-506 in intracolonically indomethacin-treated rats: 24 mg/kg of indomethacin, administered intracolonically for two days, caused gastric ulcers and two types of small intestinal ulcers (longitudinal ulcers and scattered small ulcers). Pretreatment with intraperitoneal immunosuppressants reduced the size of gastric ulcers. Both cyclosporin (10 mg/kg) and FK-506 (1 mg/kg, 2 mg/kg) treatments significantly reduced the incidence and the length of the longitudinal ulcers of the small intestine when compared to the vehicle-treated controls, whereas prednisolone (20 mg/kg) did not show any preventive effect. Furthermore, the number of small scattered ulcers of the small intestine was significantly reduced by the high dose of FK-506 (2 mg/kg), but not by cyclosporin or prednisolone. These findings indicate that immunosuppressants have protective and antiinflammatory effects in indomethacin-induced gastroenteropathy, suggesting that cytokines may be important mediators in the pathogenesis of enteropathy induced by nonsteroidal antiinflammatory drugs.
非甾体抗炎药诱发肠道溃疡的机制尚不清楚。为评估免疫抑制剂对吲哚美辛诱发的胃肠道损伤是否具有预防作用，我们研究了泼尼松龙、环孢素及新开发的免疫抑制剂FK-506对经结肠内给予吲哚美辛处理的大鼠的影响：结肠内给予24mg/kg吲哚美辛，连续两天，可导致胃溃疡及两种类型的小肠溃疡（纵行溃疡和散在小溃疡）。腹腔注射免疫抑制剂进行预处理可减小胃溃疡的面积。与给予赋形剂的对照组相比，环孢素（10mg/kg）和FK-506（1mg/kg、2mg/kg）治疗均显著降低了小肠纵行溃疡的发生率和长度，而泼尼松龙（20mg/kg）未显示出任何预防作用。此外，高剂量的FK-506（2mg/kg）可显著减少小肠散在小溃疡的数量，但环孢素或泼尼松龙则无此作用。这些发现表明，免疫抑制剂在吲哚美辛诱发的胃肠病中具有保护和抗炎作用，提示细胞因子可能是非甾体抗炎药诱发肠病发病机制中的重要介质。
