噁唑酮与三硝基苯磺酸联用诱导小鼠慢性溃疡性结肠炎模型

Chronic Ulcerative Colitis Model Induced by Oxazolone and 2,4,6-Trinitrobenzene Sulfonic Acid in Mice

目的:采用噁唑酮(oxazolone,OXZ)与2,4,6-三硝基苯磺酸(2,4,6-trinitrobenzene sulfonic acid,TNBS)结合诱导小鼠慢性溃疡性结肠炎模型。方法:取24只健康成年雄性昆明小鼠,随机分为两组,正常对照组(N组,n=12),模型组(M组,n=12),按照一定的周期诱导方法对小鼠进行OXZ与TNBS灌肠,并每天记录小鼠精神状态、毛色、进食、大便情况并检测小鼠疾病活动指数(disease activity index,DAI)。造模周期结束之后,N组与M组每周每组处死三只小鼠,连续处死4周分别记为N_1、N_2、N_3、N_4、M_1、M_2、M_3和M_4组。分离结肠,测定小鼠结肠组织大体评分(colon macroscopic damage index,CMDI)以及结肠湿重指数(colon index,CI);采用免疫组化技术检测病变部位白细胞介素-4(interleukin-4,IL-4)和肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)的水平。结果:正常组小鼠各项评分稳定,M_1、M_2、M_3和M_4模型组小鼠各项评分均显著高于正常组。结论:噁唑酮与2,4,6-三硝基苯磺酸联用可成功诱导出更接近人类慢性溃疡性结肠炎的小鼠模型,病变可维持一月。

Objective：To establish the chronic ulcerative colitis model induced by oxazolone and 2,4,6-trinitrobenzene sulfonic acid together in mice. Methods：24 healthy male Kunming mice were randomly divided into two groups：normal control group （N group,n=12）, model group （M group,n=12）. The mice were treated with OXZ and TNBS according to a certain cycle induction method by rectally administration, and the mental state, and the condition of the fur color, eating and defecation were recorded every day, and the disease activity index （disease activity index, DAI） was detected every day as well. Three mice were killed in N group and M group respectively every week, which was recorded N1, N2, N3, N4, M1, M2, M3 and M4 group after the modeling cycle. Meanwhile the colon was separated out, and the CMDI and the CI was determined. The level of the IL-4 and TNF-α detected in immunohistochemlcal teclamque was confirmed. Results： The scores of normal mice were stable, and the scores of M1, M2, M3 and M4 model groups were significantly higher than those of normal group. Conclusion：The chronic ulcerative colitis model induced by oxazolone and 2,4,6-trinitrobenzene sulfonic acid together in mice were established successfully. The pathological characteristics are closer to the human chronic ulcerative colitis and can be kept for a month at least.