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首页> 外文期刊>Digestive Diseases and Sciences >Inhibition of TNF-α Improves Indomethacin-Induced Enteropathy in Rats by Modulating iNOS Expression
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Inhibition of TNF-α Improves Indomethacin-Induced Enteropathy in Rats by Modulating iNOS Expression

机译:TNF-α的抑制通过调节iNOS的表达改善吲哚美辛诱导的大鼠肠病

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TNF-α, including other proinflammatory cytokines alone or in combination, induces iNOS expression and upregulates inflammatory responses. We evaluated the relationship between TNF-α and iNOS expression in indomethacin-induced jejunoileitis in male Sprague–Dawley rats. Rats were fed a daily dose of a phosphodiesterase inhibitor—either theophylline or pentoxifylline—for 2 days. Jejunoileitis was induced with two subcutaneous injections of indomethacin (7.5 mg/kg) 24 hr apart and theophylline or pentoxifylline continued for 12 hr or 4 days. Other rats received a single intraperitoneal injection of anti-TNF-α monoclonal antibody (TNF-Ab) 30-min before indomethacin. At 4 days TNF-Ab, theophylline, or pentoxifylline treatment significantly decreased indomethacin-induced ulceration, myeloperoxidase activity, and disease activity index. Although indomethacin significantly increased serum TNF-α and nitrateitrite levels over the control value as early as 12 hr, iNOS expression was detected only after 4 days. Serum IL-1β level did not change at 12 hr but increased fourfold at 4 days. Treatment with TNF-Ab, theophylline, or pentoxifylline significantly reduced serum/tissue TNF-α, IL-1β, nitrateitrite, and iNOS expression. The downregulation of nitrateitrite by these inhibitors suggests that TNF-α modulates iNOS expression.
机译:TNF-α,包括其他单独或组合的促炎细胞因子,可诱导iNOS表达并上调炎症反应。我们评估了吲哚美辛诱导的雄性Sprague-Dawley大鼠空肠回肠炎中TNF-α与iNOS表达之间的关系。每天给大鼠喂食磷酸二酯酶抑制剂(茶碱或己酮可可碱)2天。间隔24小时两次皮下注射消炎痛(7.5 mg / kg)诱发空肠回肠炎,茶碱或己酮可可碱持续12 hr或4天。其他大鼠在消炎痛前30分钟接受腹膜内注射抗TNF-α单克隆抗体(TNF-Ab)。在第4天,TNF-Ab,茶碱或己酮可可碱治疗显着降低了消炎痛诱导的溃疡,髓过氧化物酶活性和疾病活性指数。尽管吲哚美辛早在12小时就比对照值显着增加了血清TNF-α和硝酸盐/亚硝酸盐水平,但仅在4天后才检测到iNOS表达。血清IL-1β水平在12小时不变,但在4天时增加了四倍。用TNF-Ab,茶碱或己酮可可碱治疗可显着降低血清/组织TNF-α,IL-1β,硝酸盐/亚硝酸盐和iNOS的表达。这些抑制剂对硝酸盐/亚硝酸盐的下调表明,TNF-α调节iNOS的表达。

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