急慢性溃疡性结肠炎小鼠模型的建立与比较研究

Establishment and comparison of acute and chronic ulcerative colitis mice models

目的考察葡聚糖硫酸钠(DSS)诱导小鼠慢性溃疡性结肠炎模型与噁唑酮(OXZ)诱导小鼠急性溃疡性结肠炎模型小鼠生理病理变化,为溃疡性结肠炎治疗药物开发研究中动物模型的选择提供依据。方法通过连续7周交替饮用含1%DSS饮用水以及动物正常饮水诱导C57BL/6N小鼠慢性溃疡性结肠炎;OXZ腹部涂抹致敏后,用40%乙醇溶解灌肠诱导Balb/c小鼠急性溃疡性结肠炎。模型建立后,通过疾病活动指数(DAI)评分、脏器指数、血液学检查、结肠组织HE染色、ELISA法检测TNF-α、INF-γ以及IL-10表达水平评价造模效果并对两种模型进行比较研究。结果经DSS及OXZ诱导的小鼠结肠炎(UC)模型中,模型组小鼠均出现体质量下降、稀便以及便血等UC临床症状,DAI评分显著升高(P<0.01),与对照组相比,模型小鼠胸腺指数显著减低(P<0.01)、脾脏指数显著升高(P<0.01)、结肠长度明显缩短(P<0.01)。血液学检查以及相关炎症因子检测结果均可见模型组小鼠发生炎症反应;组织病理学检查可见模型组小鼠结肠出现溃疡、炎性细胞浸润等病理特征。结论两种方法均可以诱导溃疡性结肠炎,但小鼠的生理状态与结肠病理变化有所不同,在实际实验中应根据研究目的以及药物治疗特点选择合适的模型开展实验。

Objective To investigate the physiological and pathological changes of mice models of chronic ulcerative colitis(UC)induced by DSS and acute ulcerative colitis induced by OXZ,and to provide evidence for the selection of animal model for the development of therapeutic drugs for ulcerative colitis.Methods Chronic ulcerative colitis was induced in C57BL/6N mice by alternating drinking water with or without 1%DSS for 7 consecutive weeks.Acute ulcerative colitis was induced in Balb/c mice by abdominal sensitization with OXZ combined with ethanol enema.After the establishment of the model,the modeling effect was evaluated through disease activity index(DAI)score,organ index,hematological examination,colon tissue HE staining,and ELISA detection of TNF-α,INF-γand IL-10 levels,and a comparative study was conducted between the two models.Results In the DSS and OXZ induced mouse colitis model,the model group mice showed clinical symptoms of UC such as decreased body weight,loose stools,and bloody stools.The DAI score was significantly increased(P<0.01).Compared with the control group,the thymus index of the model mice was significantly reduced,the spleen index was significantly increased,and the colon length was significantly shortened(P<0.01).The results of hematological examination and related inflammatory factor detection showed that the model group mice experienced inflammatory reactions.The histopathological examination revealed pathological features such as ulceration and inflammatory cell infiltration in the colon of the model group mice.Conclusion Both methods can induce ulcerative colitis in mice,but the physiological state of mice and the pathological changes of colon are different.In the actual experiment,appropriate model should be selected according to the research purpose and the characteristics of drug therapy.