1 Department of Therapy Validation, Fraunhofer Institute for Cell Therapy and Immunology, Leipzig, Germany.
2 AnaPath GmbH, Liestal, Switzerland.
Lab Anim. 2018 Jun;52(3):240-252. doi: 10.1177/0023677217742681. Epub 2017 Dec 1.
Inflammatory bowel diseases (IBD) are chronic relapsing disorders of the gastrointestinal tract. Several mouse models for IBD are available, but the acute dextran sulfate sodium (DSS)-induced colitis model is mostly used for preclinical studies. However, this model lacks chronicity and often leads to significant loss of mice. The aim of this study was to establish a refined and translationally relevant model of DSS chronic colitis in BALB/c mice. In the first part, we compared several standard therapeutic (ST) treatments for IBD in the acute DSS colitis model to identify the optimal treatment control for a DSS colitis model as compared to literature data. In the second part, we tested the two most effective ST treatments in a refined model of chronic DSS colitis. Cyclosporine A (CsA) and 6-thioguanine (6-TG) caused considerable reduction of clinical scores in acute DSS colitis. The clinical outcome was confirmed by the results for colon length and by histopathological evaluation. Moreover, CsA and 6-TG considerably reduced mRNA expression of several pro-inflammatory cytokines in spleen and colon. Both compounds also showed a substantial therapeutic effect in the refined model of chronic DSS colitis with regard to clinical scores and histopathology as well as the expression of inflammatory markers. The refined model of chronic DSS colitis reflects important features of IBD and is well suited to test potential IBD therapeutics.
炎症性肠病（IBD）是一种慢性复发性胃肠道疾病。有几种用于 IBD 的小鼠模型，但急性葡聚糖硫酸钠（DSS）诱导的结肠炎模型大多用于临床前研究。然而，这种模型缺乏慢性期，并且经常导致大量小鼠死亡。本研究旨在建立一种改良的、具有转化相关性的 BALB/c 小鼠 DSS 慢性结肠炎模型。在第一部分，我们比较了几种用于急性 DSS 结肠炎模型的标准治疗（ST）方法，以确定与文献数据相比，DSS 结肠炎模型的最佳治疗对照。在第二部分，我们在慢性 DSS 结肠炎的改良模型中测试了两种最有效的 ST 治疗方法。环孢素 A（CsA）和 6-巯基嘌呤（6-TG）在急性 DSS 结肠炎中显著降低了临床评分。结肠长度和组织病理学评估的结果证实了临床结果。此外，CsA 和 6-TG 还显著降低了脾脏和结肠中几种促炎细胞因子的 mRNA 表达。这两种化合物在慢性 DSS 结肠炎的改良模型中也显示出了显著的治疗效果，包括临床评分、组织病理学和炎症标志物的表达。慢性 DSS 结肠炎的改良模型反映了 IBD 的重要特征，非常适合测试潜在的 IBD 治疗方法。
