急性结肠炎慢性化小鼠模型的建立

Establishment of Acute Colitis in Mice Model Progresses to Chronicity

背景:改变葡聚糖硫酸钠(DSS)的浓度和作用时间可建立适当的结肠炎模型,对于进一步研究其病因和发病机制具有重要意义。目的:建立急性结肠炎慢性化的小鼠模型,并探讨其病理学特征。方法:48只C57BL/6小鼠分为模型组和正常对照组。模型组自由饮用3%DSS溶液,5d后改饮用蒸馏水3周,建立急性结肠炎慢性化模型。正常对照组饮用蒸馏水26d。每日行疾病活动指数(DAI)评分。于实验第5、12、19、26d分别处死两组各6只小鼠,行结肠大体形态观察、组织病理学评分和炎症评分。结果:造模第5d,模型组小鼠均出现腹泻、血便、体质量减轻等症状,光学显微镜下可见结肠多灶性浅溃疡,上皮缺失或少许残留,隐窝破坏,杯状细胞减少,以中性粒细胞为主的炎性细胞浸润黏膜和黏膜下层。改饮用蒸馏水3周后,小鼠体质量恢复,腹泻减轻,血便等症状消失,但仍见灶性小溃疡,伴上皮不规则再生和数量较多的炎性细胞浸润。急、慢性期肠道病变均以远段结肠为重。结论:单个循环饮用3%DSS可诱导C57BL/6小鼠发生与人类临床和病理表现相似的急、慢性结肠炎,为进一步研究结肠炎提供了新的模型系统。

Background：Changing the concentration and duration of dextran sulfate sodium （DSS） treatment can establish an ideal colitis model, which is important for studying the etiology and pathogenesis of colitis. Aims： To establish a mice model that acute colitis progresses to chronicity with DSS, and to explore its pathological characteristics. Methods： Fortyeight C57BL/6 mice were divided into model group and control group. Model group was fed with 3% DSS solution ad libitum for 5 days and followed by distilled water for 3 weeks to induce a colitis model, which progressed from the acute to chronic stage. Control group was only fed with distilled water for 26 days. Disease activity index （DAI） of all the mice was evaluated daily. The mice were killed separately on the 5th, 12nd, 19th and 26th day, macroscopic, histopathological and inflammatory score of the colon were also evaluated. Results： At the 5th day, diarrhea, bloody stool and loss of body weight occured in model group. At this stage, the histopathological changes in the colon showed multifocal superficial ulcers with predominant neutrophil infiltration in mucosa and submucosa, marked loss of epithelium with destruction of crypts and reduction of goblet cells. Three weeks after cessation of feeding DSS, body weight recovered, the symptoms as diarrhea and bloody stool diminished, but the colon still showed focal small ulcers, with irregular regeneration of epithelium and infiltration of numerous inflammatory cells. Lesions in the distal colon were more severe in both acute and chronic phases. Conclusions： C57BL/6 mice fed with 3% DSS solution for 5 days and followed by distilled water for 3 weeks may establish an ideal acute and chronic colitis model, of which clinical and pathological changes are similar with those of human colitis, thus provides a new colitis model for further studies.