Chemically induced mouse models of acute and chronic intestinal inflammation
Chemically induced mouse models of acute and chronic intestinal inflammation
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DOI：
10.1038/nprot.2017.044
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发表时间：
2017-07-01
期刊：
影响因子：
14.8
通讯作者：
Neurath, Markus F.
中科院分区：
文献类型：
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作者：
Wirtz, Stefan;Popp, Vanessa;Neurath, Markus F.
炎症性肠病 (IBD) 会导致腹泻和腹痛，并可能导致组织纤维化和狭窄等进一步的潜在并发症。动物模型有助于了解 IBD 的免疫发病机制和设计新的治疗概念。在此，我们介绍了 2007 年针对 2,4,6-三硝基苯磺酸 (TNBS)、恶唑酮和葡聚糖硫酸钠 (DSS) 诱导的急性和慢性结肠炎关键模型发布的方案的更新版本。该协议更新描述了修改该技术的现有协议的改编。该协议已用于生成改进的小鼠模型，更好地反映人类 IBD 的性质。在 TNBS 和恶唑酮结肠炎模型中，局部施用半抗原试剂会导致 T 细胞介导的针对半抗原化蛋白和管腔抗原的免疫。相比之下，为了生成 DSS 结肠炎模型，小鼠口服 DSS，导致上皮细胞死亡，损害屏障功能并引起随后的炎症。急性结肠炎模型的分析可以在1-2周内完成，而慢性模型的分析可能需要2-4个月。急性模型的优点在于它们基于对短期屏障改变、先天免疫效应和耀斑的分析。慢性模型的优点是它们可以更好地了解适应性免疫和肿瘤和组织纤维化等并发症。该协议需要实验动物研究的基本技能。
Inflammatory bowel diseases (IBDs) result in diarrhea and abdominal pain with further potential complications such as tissue fibrosis and stenosis. Animal models help in understanding the immunopathogenesis of IBDs and in the design of novel therapeutic concepts. Here we present an updated version of a protocol we published in 2007 for key models of acute and chronic forms of colitis induced by 2,4,6-trinitro-benzene sulfonic acid (TNBS), oxazolone and dextran sulfate sodium (DSS). This protocol update describes an adaptation of the existing protocol that modifies the technique. This protocol has been used to generate improved mouse models that better reflect the nature of IBDs in humans. In TNBS and oxazolone colitis models, topical administration of hapten reagents results in T-cell-mediated immunity against haptenized proteins and luminal antigens. By contrast, to generate DSS colitis models, mice orally receive DSS, causing death of epithelial cells, compromising barrier function and causing subsequent inflammation. The analysis of the acute colitis models can be performed within 1-2 weeks, whereas that of the chronic models may take 2-4 months. The strengths of the acute models are that they are based on the analysis of short-lasting barrier alterations, innate immune effects and flares. The advantages of the chronic models are that they may offer better insight into adaptive immunity and complications such as neoplasia and tissue fibrosis. The protocol requires basic skills in laboratory animal research.