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Zinc deficiency induces dysregulation of cytokine productions in an experimental colitis of rats

机译:锌缺乏诱导实验性结肠炎大鼠细胞因子产生失调

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Dextran sulfate sodium (DSS)-induced colitis is an experimental model of ulcerative colitis, although the precise mechanism has not yet been elucidated. We investigate whether Zn deficiency affects the pathogenesis of colitis induced by DSS with a focus on immune responses. Male WKAH/Hkm Slc rats were fed either a Zn-adequate (ZA, 30 mg Zn/kg diet) as a control or Zndeficient (ZD, 5 mg Zn/kg diet) diet for 21 days and then treated with 2% DSS via deionized drinking water for 7 days. The disease activity index (DAI) was recorded daily throughout DSS treatment. Serum Zn concentrations were significantly lowered in rats fed the ZD diet than those fed the ZA diet at day 7 and 14. Surprisingly, DSS treatment considerably reduced the serum Zn in both groups. The rats fed the ZD diet showed exacerbated colitis based on clinical outcomes, including weight loss, increased DAI, and shortened colon length. An in vitro study corroborated these results, showing that a large amount of TNFα was induced by rat mesenteric leukocytes in response to lipopolysaccharide in ZD medium, but not in ZA medium. These results indicate that a modulation of TNFα production due to Zn deficiency influences disease activity in DSS-induced colitis. In addition, more attention should be given to Zn for prevention of colitis.
机译:硫酸右旋糖酐钠(DSS)引起的结肠炎是溃疡性结肠炎的实验模型,尽管其确切机制尚未阐明。我们调查锌缺乏症是否会影响DSS诱发的结肠炎的发病机理,重点是免疫反应。给雄性WKAH / Hkm Slc大鼠饲喂充足的锌(ZA,30 mg Zn / kg饮食)作为对照或缺锌(ZD,5 mg Zn / kg饮食)饮食21天,然后通过2%DSS去离子水饮用7天。在整个DSS治疗期间每天记录疾病活动指数(DAI)。在第7天和第14天,饲喂ZD饮食的大鼠的血清锌浓度显着低于饲喂ZA饮食的大鼠。令人惊讶的是,DSS处理可显着降低两组的血清锌。喂养ZD饮食的大鼠根据临床结果(包括体重减轻,DAI增加和结肠长度缩短)显示出加剧的结肠炎。一项体外研究证实了这些结果,表明大鼠肠系膜白细胞在ZD培养基而非ZA培养基中响应脂多糖诱导了大量的TNFα。这些结果表明由于锌缺乏引起的TNFα产生的调节影响DSS诱导的结肠炎中的疾病活性。另外,应更加注意锌以预防结肠炎。

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