A COMPARATIVE-ANALYSIS OF 2 MODELS OF COLITIS IN RATS
A COMPARATIVE-ANALYSIS OF 2 MODELS OF COLITIS IN RATS
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DOI：
10.1016/0016-5085(92)91710-l
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发表时间：
1992-05-01
期刊：
影响因子：
29.4
通讯作者：
GRISHAM, MB
中科院分区：
文献类型：
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作者：
YAMADA, T;MARSHALL, S;GRISHAM, MB
在大鼠中产生的结肠炎的两种模型在过去几年中受到显著关注，这两种模型是乙酸和三硝基苯磺酸（TNBS）模型。本研究的目的是量化和比较由乙酸、乙醇（溶剂）、乙醇加TNBS（未缓冲，pH 1.0）和乙醇加TNBS（pH 7.4）诱导的粘膜渗透性、上皮损伤和炎症之间的时间关系。获得的数据表明，这四种刺激物诱导的炎症是由于对结肠上皮和结肠粘膜的腐蚀性损伤所致，通过粘膜渗透性和组织含水量的快速和显著增加以及组织学分析进行测量。TNBS的有害性质在单独的一系列研究中得到证实，这些研究表明，在不存在乙醇的情况下，缓冲的TNBS（pH 7.4）对培养的大鼠肠上皮细胞单层有毒。仅在初始损伤1-2天后，观察到典型炎症的迹象，包括结肠髓过氧化物酶活性（中性粒细胞浸润）和结肠重量的增加以及充血和粘膜溃疡。虽然乙醇加TNBS（pH 1.0或7.4）在灌肠后1-2周倾向于产生比乙酸或乙醇组更高的粘膜渗透性（上皮细胞损伤），但发现仅乙醇加TNBS（pH 7.4）渗透性显著增强。此外，在灌肠后1-2周，所有四组均显示结肠髓过氧化物酶活性和结肠重量显著升高。这表明，这些模型的结肠炎是有用的研究事件发生时的炎症和修复。然而，这些模型在理解人类炎症性肠病中引发肠道炎症的事件方面可能具有显著的局限性。
Two models of colitis produced in rats that have received significant attention over the past few years are the acetic acid and trinitrobenzene sulfonic acid (TNBS) models. The objective of this study was to quantify and compare the temporal relationship among mucosal permeability, epithelial injury, and inflammation induced by acetic acid, ethanol (vehicle), ethanol plus TNBS (unbuffered, pH 1.0), and ethanol plus TNBS (pH 7.4). Data obtained show that the inflammation induced by these four irritants results from caustic injury to the colonic epithelium and interstitium as measured by the rapid and dramatic increases in mucosal permeability and tissue water content as well as by histological analysis. The injurious nature of TNBS was confirmed in a separate series of studies showing that buffered TNBS (pH 7.4), in the absence of ethanol, is toxic to cultured rat intestinal epithelial cell monolayers. Only after 1–2 days of the initial insult, were signs of classical inflammation observed, including increases in colonic myeloper-oxidase activity (neutrophil infiltration) and colon weight as well as hyperemia and mucosal ulcerations. Although ethanol plus TNBS (pH 1.0 or 7.4) tended to produce higher mucosal permeabilities (epithelial cell injury) at 1–2 weeks after the enemas than acetic acid or ethanol groups, only the ethanol plus TNBS (pH 7.4) permeabilities were found to be significantly enhanced. In addition, all four groups showed significant elevations in colonic myeloperoxidase activity and colon weight at 1–2 weeks after enema. It is suggested that these models of colitis are useful to study events that occur at the time of inflammation and repair. However, these models may have significant limitations in understanding events that initiate inflammation of the intestine in human inflammatory bowel disease.