具有临床代表性的艰难梭菌感染小鼠稳定模型的构建

Establishment of stable and clinically representative mouse models of Clostridium difficile infection

目的构建临床代表性好、稳定性佳的艰难梭菌感染小鼠模型,为艰难梭菌感染相关疾病提供研究工具。方法选择C57BL/6、BALB/c、昆明小鼠,经抗生素诱导后,分别予以不同浓度(108 CFU/mL^10^(10) CFU/mL)的临床分离菌株混悬液灌胃,观察不同品系小鼠不同时间点腹泻、全身情况及结肠组织病理学变化。结果灌菌后,BALB/c小鼠10^(10) CFU/mL浓度组全部出现腹泻,死亡率为16.7%;其他实验组小鼠腹泻程度差异较大或仅部分出现轻度腹泻。腹泻小鼠表现为稀烂便甚至水样便和湿尾现象,体重减轻,肠道病理显示结肠黏膜充血水肿伴炎性细胞浸润。结论经5种抗生素灌胃9d+克林霉素腹腔注射诱导,10^(10) CFU/mL艰难梭菌活菌混悬液灌胃后构建的BALB/c小鼠艰难梭菌感染模型最稳定。

Objective To build mouse models of Clostridium difficile infection with clinical representativeness and good stability,and provide suitable tools for researches on the infection of Clostridium difficile.Methods 3different species of mice（C57BL/6mice,BALB/c mice and KM mice）were treated with antibiotics and then challenged with different concentrations of Clostridium difficile suspension by gavage.The symptom of diarrhea,general situation and pathological changes of colonic tissues were observed.Results After gavage,all the BALB/c mice in the 10^（10） CFU/mL concentration group developed diarrhea,with a mortality rate of 16.7%.The diarrhea symptoms of mice in other experimental groups varied in severity or even were mild and only seen in some of the mice.The mice with diarrhea had loose or even watery stool,wet tail,weight loss and reduced food intake.Histological examination showed congestion,hemorrhage and neutrophil infiltration of the mucosa in dead mice.Conclusion BALB/c mice which were induced by gavage with five antibiotics for 9days and intraperitoneal injection with clindamycin,then gavaged with 10^（10） CFU/mL of Clostridium difficile bacterial suspension are the most stable models for Clostridium difficile associated diarrhea.