Tran C D, Ball J M, Sundar S, Coyle P, Howarth G S
Gastroenterology Unit, Children, Youth and Women's Health Service, 72 King William Road, North Adelaide, SA 5006, Australia.
Dig Dis Sci. 2007 Sep;52(9):2113-21. doi: 10.1007/s10620-007-9765-9. Epub 2007 Apr 5.
Zinc (Zn) and its binding protein metallothionein (MT) have been proposed to suppress the disease activity in ulcerative colitis. To determine the role of Zn and MT in the dextran sulfate sodium (DSS)-induced model of colitis in mice, a DSS dose-response study was conducted in male C57BL/6 wild-type (MT+/+) and MT-null (MT-/-) mice by supplementing 2%, 3%, and 4% DSS in the drinking water for 6 days. In the intervention study, colitis was induced with 2% DSS, Zn (24 mg/ml as ZnO) was gavaged (0.1 ml) daily, concurrent with DSS administration, and the disease activity index (DAI) was scored daily. Histology, MT levels, and myeloperoxidase (MPO) activity were determined. DAI was increased (P<0.05) by 16% and 21% with 3% and 4% concentrations of DSS, respectively, compared to 2%, evident after 5 days of DSS administration. MPO activity was increased in MT+/+ compared to MT-/- mice and those receiving DSS. Zn administration had a 50% (P<0.05) lower DAI compared to DSS alone. Zn partially prevented the distal colon of MT+/+ by 47% from DSS-induced damage compared to MT-/- mice. MT did not prevent DSS-induced colitis and Zn was partially effective in amelioration of DSS-induced colitis.
锌（Zn）及其结合蛋白金属硫蛋白（MT）被认为可抑制溃疡性结肠炎的疾病活动。为确定锌和金属硫蛋白在葡聚糖硫酸钠（DSS）诱导的小鼠结肠炎模型中的作用，通过在饮用水中添加2%、3%和4%的DSS持续6天，对雄性C57BL/6野生型（MT+/+）和MT基因敲除（MT-/-）小鼠进行了DSS剂量反应研究。在干预研究中，用2%的DSS诱导结肠炎，每天灌胃给予锌（以氧化锌计为24毫克/毫升，0.1毫升），与DSS给药同时进行，每天对疾病活动指数（DAI）进行评分。测定组织学、MT水平和髓过氧化物酶（MPO）活性。与2%的DSS相比，3%和4%浓度的DSS分别使DAI增加了16%和21%（P<0.05）,在给予DSS 5天后明显。与MT-/-小鼠和接受DSS的小鼠相比，MT+/+小鼠中的MPO活性增加。与单独使用DSS相比，给予锌使DAI降低了50%（P<0.05）。与MT-/-小鼠相比，锌使MT+/+小鼠的远端结肠免受DSS诱导损伤的比例达47%。MT不能预防DSS诱导的结肠炎，而锌在改善DSS诱导的结肠炎方面有部分效果。
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