右旋葡聚糖硫酸钠小鼠溃疡性结肠炎动物模型建立方法探讨

Establishment of Dextran Sodium Sulfate-induced Mice Ulcerative Colitis Model

背景:溃疡性结肠炎(UC)的病因和发病机制尚不十分清楚,建立适当的结肠炎动物模型对于研究其病因和发病机制具有重要意义。目的:探讨右旋葡聚糖硫酸钠(DSS)诱发的小鼠UC动物模型的建立方法。方法:将18只雄性BALB/C小鼠随机分为3组,实验组中一组饮用5％DSS溶液7天诱发急性结肠炎,另一组饮用5％DSS溶液7天后继续饮用蒸馏水14天诱发慢性结肠炎;对照组饮用蒸馏水。观察小鼠每日的体重、大便性状和隐血情况以及结肠大体形态和组织病理学改变。结果:饮用5％DSS溶液7天,BALB/C小鼠可发生腹泻、血便等症状,全结肠表现为以隐窝破坏为特征的多灶性小溃疡,伴中性粒细胞为主的急性炎症细胞浸润。停止饮用5％DSS溶液14天后,BALB/C小鼠的腹泻、血便等症状消失,全结肠表现为更局限的灶性小溃疡伴邻近上皮细胞再生、修复,以及突出的隐窝扭曲变形伴以淋巴、单核细胞为主的慢性炎症细胞浸润。急、慢性期肠道病变均以远段结肠为重。结论:单次使用DSS诱发的小鼠急、慢性结肠炎是一种较理想的UC动物模型,可作为研究UC发病机制和药物治疗较理想的工具。

Background: The causes and mechanisms of ulcerative colitis (UC) are still unknown, so it is important to establish an ideal colitis model for studying the etiology and pathogenesis of UC. Aims: To discuss the method to establish dextran sodium sulfate (DSS)-induced mice UC model. Methods: Eighteen male BALB/C mice were randomly divided into three groups. The experimental groups were fed with 5% DSS solution for 7 days and 5% DSS solution for 7 days followed by distilled water for 14 days to induce acute and chronic colitis, respectively. The control group was only fed with distilled water. In all animals, daily weight, daily stool consistency and occult blood were observed, and the macroscopic and histopathological changes of the colon were also evaluated. Results: BALB/C mice treated with 5% DSS solution for 7 days developed diarrhea and bloody stool. At this stage, the histopathological changes in the entire colon showed multiple ulcer foci with predominant neutrophil infiltration. Treated with 7 days of 5% DSS solution followed by 14 days of distilled water, the symptoms as diarrhea and bloody stool diminished, and the colon showed more localized small ulcer foci with the regeneration of adjacent epithelial cells histopathologically. In addition, distorted crypts with lymphocytes, monocytes and other chronic inflammatory cells infiltration were also predominant. The lesions in the distal colon were more serious than those in the proximal and middle colon in both acute and chronic models. Conclusions: The acute and chronic mice colitis induced by feeding DSS is an ideal model of UC, which might be served for investigation of the pathogenesis and drug treatment effect of UC.