EXPERIMENTAL-MODELS OF INFLAMMATORY BOWEL-DISEASE
EXPERIMENTAL-MODELS OF INFLAMMATORY BOWEL-DISEASE
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DOI：
10.1016/0016-5085(95)90599-5
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发表时间：
1995-10-01
期刊：
影响因子：
29.4
通讯作者：
RIDDELL, RH
中科院分区：
文献类型：
--
作者：
ELSON, CO;SARTOR, RB;RIDDELL, RH
炎症性肠病（IBD），克罗恩病和溃疡性结肠炎，是一种病因不明的多因素疾病。虽然确切的发病机制知之甚少，但有证据表明，它涉及免疫系统，遗传易感性和环境之间的相互作用，最明显的是细菌植物群。启动与进展和慢性化的机制可能是不同的。实验动物模型允许研究早期事件，解剖不同成分之间的相互作用，并识别免疫过程和基因，这些免疫过程和基因以人类不可能的方式决定易感性。这些疾病的复杂性在任何更简单的系统中都是不可重现的，包括简化的组织培养系统，尽管后者可以有效地用于研究对IBD重要的选定的、高度定义的过程。用实验模型获得的结果产生了新的范例来测试患者;它们补充和扩展了人类研究，但并没有取代它们。本报告部分基于IBD实验模型研讨会，讨论了各种常用模型和一些最近开发的模型。这篇综述的前提是，IBD的模型没有对错之分，但不同的模型在其相对用途上确实有所不同，这篇综述的目的是定义不同的模型告诉我们什么，以及它们在IBD研究中最有用的地方。为此，导致IBD的多种因素被人为地分为六个主要组成部分，即遗传易感性、环境因素、获得性免疫、先天免疫、非特异性炎症和伤口愈合。这些主要组件中的每一个都可以细分为表1所示的各种子组件。前三个组成部分可以被认为是代表过程中的早期事件，最后三个组成部分代表炎症和修复的最终共同途径。特定研究的适当模式完全取决于所处理的问题。例如，许多模型已被用于测试可能用于患者的新抗炎药物的使用;仅涉及非特异性炎症的简单，可重复的模型可能足以用于此目的。遗传易感性或获得性免疫的研究必然涉及更复杂的模型，在这些模型中可以研究这些成分。作为指导，提供图1以帮助研究者关注哪种模型可能对研究表1中所示的IBD的各种组分最有用。不同模型的建议有用性并不意味着是教条式的，未来的进展几乎肯定会修改它;然而，它是作为一个方便的出发点感兴趣的调查。在下面的文本和表格中，简要讨论了可用的实验模型，包括用于生成模型的方法，其病理学，技术陷阱或问题，优点，缺点以及如何使用它的评论。为了便于讨论，这些模型被任意归类并汇总在表格中。本报告旨在提供一个参照框架，而不是详尽无遗的审查。
T he inflammatory bowel diseases (IBDs), Crohn's dis-ease and ulcerative colitis, are multifactorial disorders whose etiology remains unknown. Although the exact pathogenesis is poorly understood, there is evidence that it involves interactions among the immune system, genetic susceptibility, and the environment, most notably the bacterial flora. Mechanisms underlying initiation vs. progression and chronicity may well be distinct. Experimental animal models allow study of early events, dissection of the interactions among different components, and identification of immunologic processes and genes that determine susceptibility in ways that are not possible in humans. The complexity of these disorders is not reproducible in any simpler system, including reductionist tissue culture systems, although the latter can be effectively exploited to study selected, highly defined processes that are important to IBD. The results obtained with experimental models generate new paradigms to test in patients; they complement and expand studies in humans but do not replace them. This report is based in part on a workshop on experimental models of IBD at which both a variety of models in common use and some recently developed models were discussed. The premise of this review is that there is no right or wrong model of IBD but that the different models do differ in their relative use, and the purpose of this review is to define what the different models have told us and where they seem most useful for the study of IBD. Toward this end, the multiple factors contributing to IBD have been artificially divided into six major components, namely, genetic susceptibility, environmental factors, acquired immunity, innate immunity, nonspecific inflammation, and wound healing. Each of these major components can be subdivided into a variety of subcomponents as shown in Table 1. The first three components can be thought of as representing early events in the process and the last three as representing a final common pathway of inflammation and repair. The appropriate model for a given study depends entirely on the question being addressed. For example, many of the models have been used to test the use of new anti-inflammatory drugs that might be used in patients; simple, reproducible models involving only nonspecific inflammation may suffice for this purpose. Studies of genetic susceptibility or acquired immunity necessarily involve more complex models in which these components can be studied. As a guide, Figure 1 is provided to help investigators focus on which model might be most useful to study the various components of IBD shown in Table 1. The proposed usefulness for the different models is not meant to be dogmatic, and future progress will almost certainly modify it; however, it is presented as a convenient starting place for the interested investigator. In the text and tables that follow, there is a brief discussion of the available experimental models, including the method used to generate the model, its pathology, technical pitfalls or problems, advantages, disadvantages, and commentary on how it has been used. To facilitate this discussion, the models are arbitrarily clustered into categories and summarized in tables. This report is intended to provide a frame of reference rather than an exhaustive review.