Alican I, Coşkun T, Corak A, Yeğen B C, Oktay S, Kurtel H
Department of Physiology, Marmara University, School of Medicine, Istanbul, Turkey.
Inflamm Res. 1995 Apr;44(4):164-8. doi: 10.1007/BF01782814.
Nonsteroidal anti-inflammatory drugs (NSAIDs) cause clinically important gastric damage by several mechanisms. In order to evaluate the role of neutrophil infiltration in lesion formation, tissue myeloperoxidase activities were assessed in different gastric layers of the stomach both in rats with normal neutrophil levels and in neutropenic rats. Sprague-Dawley rats were treated either with indomethacin (Indo; 25 mg/kg, s.c.) or the vehicle. A group of rats were made neutropenic by administration of methotrexate (MTX; 2.5 mg/kg i.p.) once a day for 3 days. The stomachs were removed for the determination of lesion index, glutathione, lipid peroxide levels, protein oxidation and tissue myeloperoxidase activities. MTX treatment appeared to reduce neutrophil infiltration significantly while producing insignificant effects on eosinophils and macrophages. Indo administration caused multiple gastric lesions and treatment with MTX significantly reduced lesion index. In rats treated with Indo, neither glutathione nor LP levels showed any significant changes but the protein oxidation was significantly higher than that of other groups. The MPO level of gastric mucosa was increased in Indo-treated rats and reversed by MTX pretreatment. The results of the present study indicate that neutrophil infiltration in the gastric mucosa of rats may be involved in the pathogenesis of NSAID-induced gastric mucosal injury, but no correlation was found between lesion formation and protein oxidation in the gastric mucosa.
非甾体抗炎药（NSAIDs）通过多种机制导致具有临床重要性的胃损伤。为了评估中性粒细胞浸润在损伤形成中的作用，在中性粒细胞水平正常的大鼠和中性粒细胞减少的大鼠的胃不同层次中评估了组织髓过氧化物酶活性。将Sprague-Dawley大鼠用吲哚美辛（Indo；25mg/kg，皮下注射）或赋形剂处理。一组大鼠通过每天腹腔注射甲氨蝶呤（MTX；2.5mg/kg）共3天制成中性粒细胞减少。取出胃以测定损伤指数、谷胱甘肽、脂质过氧化物水平、蛋白质氧化和组织髓过氧化物酶活性。MTX处理似乎显著减少了中性粒细胞浸润，而对嗜酸性粒细胞和巨噬细胞产生的影响不显著。给予Indo导致多处胃损伤，MTX处理显著降低了损伤指数。在用Indo处理的大鼠中，谷胱甘肽和LP水平均未显示任何显著变化，但蛋白质氧化显著高于其他组。Indo处理的大鼠胃黏膜的MPO水平升高，MTX预处理可使其逆转。本研究结果表明，大鼠胃黏膜中的中性粒细胞浸润可能参与了NSAID诱导的胃黏膜损伤的发病机制，但未发现胃黏膜损伤形成与蛋白质氧化之间存在相关性。
