DSS与TNBS诱导大鼠实验性结肠炎模型的对比研究

摘要

Background:As the empirical studies on human body are restricted extremely,the establishment and selection of suitable animal models are important for researches on ulcerative colitis( UC ). Aims:To compare the symptoms and colonic pathology of rat models with experimental colitis induced by dextran sulfate sodium( DSS ) and trinitrobenzene sulfonic acid( TNBS),so as to provide a reference for selecting animal models in UC-related studies. Methods:Drinking 4% DSS freely for 7 days or intrarectal administration of single dose 100 mg/kg TNBS-50% ethanol were used to establish experimental colitis model in Sprague-Dawley rats. The disease activity index( DAI)was assessed dynamically during the course of experiment. The whole colon was removed in batches for measurements of colonic damage score and activity of myeloperoxidase(MPO)at different time points. Results:The DAI score reached the peak at the 7th day and the 2nd day in DSS group and TNBS group,respectively,and decreased gradually afterwards. Six and one deaths occurred during the experimental course in DSS and TNBS groups,respectively. In DSS group,the duration of inflammation was short,the colonic injury was moderate and recovered after drug withdrawal. At the 18th day,the colonic damage score and MPO activity was 0. 25 ± 0. 50 and(0. 80 ± 0. 33)U/g,respectively,and no significant differences were seen between DSS group and normal control group. In TNBS group,the duration of inflammation was longer and the colonic injury was more severe. At the 21st day,the colonic damage score and MPO activity was 3. 60 ± 0. 55 and( 1. 60 ± 0. 39 ) U/g, respectively,and chronic inflammation was observed histologically. Conclusions:Both DSS and TNBS can induce experimental colitis model in rats. The course of TNBS-induced colitis model presents a transformation of acute to chronic inflammation,and may be more suitable for treatment-related studies of UC.%背景：鉴于人体实验受到诸多限制，建立、选择合适的动物模型对于溃疡性结肠炎（ UC）的研究具有重要意义。目的：比较葡聚糖硫酸钠（ DSS）和三硝基苯磺酸（ TNBS）诱导的大鼠实验性结肠炎模型的症状和结肠病理改变，以期为UC相关研究动物模型的选择提供参考。方法：予Sprague-Dawley大鼠自由饮用4% DSS 7 d或予100 mg/kg TNBS-50%乙醇单次灌肠建立实验性结肠炎模型，动态评估疾病活动指数（ DAI）。分批取模型大鼠全结肠标本，观察不同时点的结肠损伤评分、髓过氧化物酶（ MPO）活性等指标。结果：DSS和TNBS模型组DAI最高值分别出现在实验第7天和第2天，其后呈下降趋势，两组造模过程中分别有6只和1只大鼠死亡。DSS模型组结肠炎症持续时间短，损伤轻，停药后病变逐渐好转，18 d时结肠损伤评分和MPO活性分别为0.25±0.50和（0.80±0.33）U/g，与正常对照组相比无明显差异。TNBS模型组结肠炎症持续时间长，损伤重，21 d时结肠损伤评分和MPO活性分别为3.60±0.55和（1.60±0.39）U/g，组织学上呈现慢性炎症特征。结论：DSS和TNBS均可成功诱导大鼠实验性结肠炎模型，后者可体现急性炎症向慢性转化的动态过程，可能更适用于UC治疗相关研究。