小鼠慢性炎症性肠病模型的创建与评价

Establishment and evaluation of models of chronic inflammatory bowel disease in mice

目的构建小鼠慢性炎症性肠病(IBD)模型,为干细胞治疗研究提供实验模型。方法40只SPF雄性C57BL/6小鼠随机分为Ⅰ~Ⅳ组:Ⅰ组为空白对照组;Ⅱ组持续饲饮硫酸葡聚糖钠(DSS)5d,间隔5d依次循环;Ⅲ组持续饲饮DSS4d,间隔3d,依次循环;Ⅳ组持续饲饮DSS不间隔。监测各组的精神状态、体重、粪便等,于造模后第4、7、28d,各组随机处死3只小鼠,取结肠组织进行病理学观察和免疫组化分析。结果于造模28d,Ⅱ组病死率为100%;Ⅲ组病死率低于20%,病理组织学变化符合IBD临床特点,组织轮廓模糊,黏膜层腺体缺失,结缔组织增生,伴有淋巴细胞浸润;Ⅳ组体重迅速下降,至第9d全部死亡。结论持续给DSS4d,间隔3d依次循环,可制备符合IBD要求的小鼠模型。

Objective To establish the model of inflammatory bowel disease(IBD)in mice and provide test subjects for stem cell therapy research.Methods A total of 40 specific pathogen-free(SPF)male C57BL/6 mice were randomly divided into four groups.Group I was blank control group,groupⅡwas continuously fed with dextran sulfate sodium(DSS)for five days,followed by a 5 d interval for several cycles,groupⅢwas continuously fed with DSS for four days,followed by a 3 d interval for several cycles,and group IV was continuously fed with DSS without interval.The mental state,weight,stool and other situations were monitored for each group.In this study,three random mice from each group were sacrificed respectively four,seven,and 28 days after the establishment of model.Then the colon tissues were taken for pathological observation and immunohistochemical analysis.Results The mortality of groupⅡwas 100%at 28 days after the establishment of model,and that of groupⅢwas lower than 20%.The histopathological changes of groupⅢwere consistent with the clinical characteristics of IBD,including vague tissue contour,gland loss in the mucosal layer,connective tissue hyperplasia,and lymphocyte infiltration.The weight of the mice in group IV dropped rapidly and all mice in this group died on the ninth day.Conclusion The model of mice which meets the requirements of IBD can be established through continuously administration of DDS for four days,followed by a 3 d interval for several cycles.