Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat
Excessive Interleukin 18 Relate the Aggravation of Indomethacin-Induced Intestinal Ulcerogenic Lesions in Adjuvant-Induced Arthritis Rat
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DOI：
10.1248/bpb.b15-00375
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发表时间：
2015-10-01
影响因子：
2
通讯作者：
Ito, Yoshimasa
中科院分区：
文献类型：
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作者：
Nagai, Noriaki;Tanino, Tadatoshi;Ito, Yoshimasa
众所周知，类风湿关节炎患者服用非甾体抗炎药（NSAIDs）比其他患者更容易发生非甾体抗炎药引起的胃肠病。在这项研究中，我们证明了白介素(IL)-18的表达水平与口服吲哚美辛后佐剂性关节炎（AA）大鼠肠道溃疡性病变的加重有关。AA大鼠口服吲哚美辛（40 mg/kg），异氟醚深度麻醉24 h后处死，检查小肠黏膜。口服吲哚美辛可引起AA大鼠小肠黏膜出血性病变，治疗24 h后AA大鼠的病变评分比正常大鼠高约5.6倍。吲哚美辛给药AA大鼠小肠黏膜IL-18表达也高于正常大鼠。此外，口服吲哚美辛后AA大鼠小肠黏膜中干扰素- γ和一氧化氮水平升高。可能是AA大鼠体内IL-18的表达使小肠黏膜对吲哚美辛更加敏感，IL-18可能加重了吲哚美辛对AA大鼠肠道溃疡性病变的影响。
It is well known that rheumatoid arthritis patients taking nonsteroidal anti-inflammatory drugs (NSAIDs) are more susceptible to NSAIDs-induced gastroenteropathy in comparison with other patients. In this study we demonstrate that expression levels of interleukin (IL)-18 are related to aggravation of intestinal ulcerogenic lesions in adjuvant-induced arthritis (AA) rats following oral administration of indomethacin. AA rats were administered oral indomethacin (40 mg/kg) and killed under deep isoflurane anesthesia after 24 h. The small intestinal mucosa was then examined. Oral administration of indomethacin caused hemorrhagic lesions in the small intestinal mucosa of AA rats, and the lesion score of AA rats 24 h after indomethacin treatment was approximately 5.6-fold higher than for normal rats administered indomethacin. IL-18 expression in the small intestinal mucosa of AA rats administered indomethacin was also higher in comparison with normal rats receiving indomethacin. In addition, interferon-gamma and nitric oxide levels in the small intestinal mucosa of AA rats were increased following oral administration of indomethacin. It is possible that IL-18 expression in AA rats renders the small intestinal mucosa more sensitive to indomethacin, and that IL-18 may play a role in aggravating intestinal ulcerogenic lesions in AA rats treated with this drug.