Chemically induced mouse models of intestinal inflammation

Chemically induced mouse models of intestinal inflammation
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DOI:
10.1038/nprot.2007.41
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发表时间:
2007-01-01
期刊:
影响因子:
14.8
通讯作者:
Neurath, Markus F.
Neurath, Markus F.
中科院分区:
生物学1区
文献类型:
--
作者:
Wirtz, Stefan;Neufert, Clemens;Neurath, Markus F.

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肠道炎症的动物模型对于我们理解克罗恩病和溃疡性结肠炎的发病机制是不可或缺的,克罗恩病和溃疡性结肠炎是人类炎症性肠病的两种主要形式。在这里,我们提供了建立小鼠2,4,6-三硝基苯磺酸(TNBS),恶唑酮-和急性和慢性葡聚糖硫酸钠(DSS)结肠炎,最广泛使用的化学诱导的肠道炎症模型的协议。在前两种模型中,结肠炎是通过直肠内施用共价反应性试剂TNBS/恶唑酮诱导的,据信其诱导T细胞介导的针对半抗原修饰的自体蛋白/管腔抗原的应答。在DSS模型中,小鼠接受补充有DSS的饮用水数天,DSS似乎对基底隐窝的结肠上皮细胞直接有毒。结肠炎和急性DSS结肠炎的半抗原模型的程序可以在约2周内完成,但慢性DSS结肠炎的方案需要约2个月。
Animal models of intestinal inflammation are indispensable for our understanding of the pathogenesis of Crohn disease and ulcerative colitis, the two major forms of inflammatory bowel disease in humans. Here, we provide protocols for establishing murine 2,4,6-trinitro benzene sulfonic acid (TNBS)-, oxazolone- and both acute and chronic dextran sodium sulfate (DSS) colitis, the most widely used chemically induced models of intestinal inflammation. In the former two models, colitis is induced by intrarectal administration of the covalently reactive reagents TNBS/oxazolone, which are believed to induce a T-cell-mediated response against hapten-modified autologous proteins/luminal antigens. In the DSS model, mice are subjected several days to drinking water supplemented with DSS, which seems to be directly toxic to colonic epithelial cells of the basal crypts. The procedures for the hapten models of colitis and acute DSS colitis can be accomplished in about 2 weeks but the protocol for chronic DSS colitis takes about 2 months.