Cooper H S, Murthy S N, Shah R S, Sedergran D J
Department of Pathology and Laboratory Medicine, Hahnemann University, Philadelphia, Pennsylvania.
Lab Invest. 1993 Aug;69(2):238-49.
We undertook this study in order to fully characterize the clinical and histopathology features of the dextran sulfate sodium (DSS) model of experimental murine colitis and to discover the earliest histopathologic changes that lead to colitis.
Acute colitis was induced in Swiss-Webster mice by 7 days of oral DSS with animals sacrificed daily. Chronic colitis was induced by: (a) 7 days of oral DSS followed by 7 days of H2O (for 1, 2, and 3 cycles) and (b) 7 days of oral DSS followed by 14 and 21 days of H2O. In each experimental group, the entire colons were examined histologically and correlated with clinical symptoms.
Acute clinical symptoms (diarrhea and/or grossly bloody stool) were associated with the presence of erosions and inflammation. More importantly, the earliest histologic changes which predated clinical colitis was loss of the basal one-third of the crypt (day 3), which progressed with time to loss of the entire crypt resulting in erosions on day 5. The earliest changes were very focal and not associated with inflammation. Inflammation was a secondary phenomena and only became significant after erosions appeared. Animals treated with only 7 days of DSS followed by 14 and 21 days of H2O developed a chronic colitis with the following histologic features: areas of activity (erosions and inflammation), inactivity, crypt distortion, florid epithelial proliferation and possible dysplasia. These changes were similar to animals given 3 cycles of DSS. The clinical disease activity index correlated significantly with pathologic changes in both the acute and chronic phases of the disease.
The mechanism of DSS colitis is presently unknown. However, the finding of crypt loss without proceeding or accompanying inflammation suggests that the initial insult is at the level of the epithelial cell with inflammation being a secondary phenomena. This may be a good model to study how early mucosal changes lead to inflammation and the biology of the colonic enterocyte. Chronic colitis induced after only 7 days of DSS may serve as a useful model to study the effects of pharmacologic agents in human inflammatory disease and mechanisms of perpetuation of inflammation. Finally, we believe that this model has the potential to study the dysplasia cancer sequence in inflammatory disease.
我们开展这项研究是为了全面描述葡聚糖硫酸钠（DSS）诱导的实验性小鼠结肠炎的临床和组织病理学特征，并找出导致结肠炎的最早组织病理学变化。
通过给瑞士-韦伯斯特小鼠口服7天DSS诱导急性结肠炎，每天处死动物。慢性结肠炎通过以下方式诱导：（a）口服7天DSS，随后7天给予水（共1、2和3个周期）；（b）口服7天DSS，随后14天和21天给予水。在每个实验组中，对整个结肠进行组织学检查，并与临床症状相关联。
急性临床症状（腹泻和/或肉眼可见的血便）与糜烂和炎症的存在相关。更重要的是，早于临床结肠炎的最早组织学变化是隐窝底部三分之一的缺失（第3天），随着时间推移发展为整个隐窝缺失，导致第5天出现糜烂。最早的变化非常局限，且与炎症无关。炎症是继发现象，仅在糜烂出现后才变得明显。仅接受7天DSS治疗，随后14天和21天给予水的动物发展为慢性结肠炎，具有以下组织学特征：活动区域（糜烂和炎症）、静止区域、隐窝变形、上皮细胞显著增生以及可能的发育异常。这些变化与接受3个周期DSS治疗的动物相似。临床疾病活动指数与疾病急性和慢性阶段的病理变化显著相关。
DSS结肠炎的机制目前尚不清楚。然而，发现隐窝缺失而无炎症进展或伴随炎症表明，最初的损伤发生在上皮细胞水平，炎症是继发现象。这可能是研究早期黏膜变化如何导致炎症以及结肠肠上皮细胞生物学特性的良好模型。仅7天DSS诱导的慢性结肠炎可作为研究药物对人类炎症性疾病的影响以及炎症持续机制的有用模型。最后，我们认为该模型有潜力研究炎症性疾病中的发育异常-癌症序列。
