Zinc deficiency induces dysregulation of cytokine productions in an experimental colitis of rats
Zinc deficiency induces dysregulation of cytokine productions in an experimental colitis of rats
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DOI：
10.2220/biomedres.33.329
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发表时间：
2012-12-01
影响因子：
1.2
通讯作者：
Ishizuka, Satoshi
中科院分区：
文献类型：
--
作者：
Suwendi, Erwin;Iwaya, Hitoshi;Ishizuka, Satoshi
葡聚糖硫酸钠（DSS）诱导的结肠炎是溃疡性结肠炎的实验模型，尽管确切的机制尚未阐明。我们研究锌缺乏是否影响DSS诱导的结肠炎的发病机制，重点是免疫反应。给雄性WKAH/Hkm Sic大鼠喂食锌充足（ZA，30 mg Zn/kg饮食）作为对照或锌缺乏（ZD，5 mg Zn/kg饮食）饮食21天，然后通过去离子饮用水用2%DSS处理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，喂食ZD饮食的大鼠血清锌浓度显著低于喂食ZA饮食的大鼠。令人惊讶的是，DSS治疗大大降低了两组中的血清Zn。根据临床结果（包括体重减轻、DAI增加和结肠长度缩短），喂食ZD饮食的大鼠表现出结肠炎恶化。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培养基中对脂多糖的反应中诱导了大量TNF α，但在ZA培养基中没有。这些结果表明，在DSS诱导的结肠炎中，由于锌缺乏而调节TNF α产生影响疾病活动。此外，在预防结肠炎时应注意锌。
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 Sic rats were fed either a Zn-adequate (ZA, 30 mg Zn/kg diet) as a control or Zn-deficient (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 TNF alpha 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 TNF alpha 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.