炎症性肠炎( Inflammatory Bowel Disease, IBD)是结肠或胃肠道的非特异性慢性炎症性疾病，包括溃疡性结肠炎（ulcerative colitis，UC）和克罗恩病（Crohn’s disease，CD），有相似的临床症状包括反复发作的腹泻、腹痛、肠出血/便血、发热，体重减轻。IBD的致病机理尚不明确，研究表明易感基因、免疫系统、外界环境和肠道微生物等多种因素均与疾病发生相关。目前有多种临床前小鼠模型用于研究IBD，基于不同诱导方法得到的疾病模型具有特定的用途。葡聚糖硫酸钠（Dextran Sulfate Sodium Salt，DSS）诱导的小鼠肠炎模型是使用最广泛的化学诱导小鼠IBD模型。通过将DSS溶于饮用水中诱发急性溃疡性肠炎或者慢性结肠炎，破坏小鼠肠上皮细胞，非特异性免疫细胞释放细胞因子，最终导致黏膜屏障的完整性遭到破坏，动物表现出明显的体重减轻、稀便、便血以及粒细胞浸润现象，在临床症状和病理特征上与人类的溃疡性结肠炎极其相似。
百奥赛图在C57BL/6小鼠上建立了稳定的DSS诱导IBD疾病模型，可用于炎症性肠炎的临床前研究和药效评价。
模型制备示意图
临床评分
C57BL/6小鼠连续7天饮用含DSS的饮用水，全程记录体重变化，并进行临床评分。（A-C）各组动物体重变化趋势。（D）各组动物临床评分。实验数据显示，造模组（G2-DSS）相对于未造模组（G1-Vehicle），动物体重有所下降，且临床评分明显升高；给药组（G3-DSS-CSA low dose和G4-DSS-CSA high dose）的动物体重变化不明显，临床评分略有升高。这表明DSS诱发C57BL/6小鼠炎性肠病疾病模型造模成功，CsA对小鼠炎性肠病疾病模型的临床症状有缓解，并且呈现剂量依赖效应。
大体取材与结肠评价
DSS诱发C57BL/6小鼠炎性肠病疾病模型7天后，取结肠进行称重和测量长度。（A）结肠长度比较。（B）各组动物结肠重量与体重比值。（C）各组动物结肠重量与结肠长度比值。实验数据显示，造模组（G2-DSS）相对于未造模组（G1-Vehicle），结肠重量和长度明显异常；给药组（G3-DSS-CSA low dose和G4-DSS-CSA high dose）的结肠重量和长度相对较好。这表明CsA对DSS诱发小鼠炎性肠病疾病模型的结肠症状有所缓解。
病理分析
取DSS诱发C57BL/6小鼠炎性肠病疾病模型的结肠，将组织切片进行病理检测。（A）各组动物结肠H&E染色图示。（B）各组动物结肠病理评分。实验数据显示，造模组（G2-DSS）相对于未造模组（G1-Vehicle），肠上皮细胞受到破坏，肠道黏膜层完整性遭到破坏，炎性细胞大量浸润；而给药组（G3-DSS-CSA low dose和G4-DSS-CSA high dose）的结肠症状明显缓解，且表现出剂量效应。
综合临床评分、大体取材和结肠评价、病理分析结果，表明DSS诱发C57BL/6小鼠炎性肠病疾病模型造模成功，环孢菌素A（CsA）能够显著缓解DSS诱发炎性肠病结肠病损，且表现出剂量效应。
参考文献：
1. Elson, C.O., Sartor, R.B., Tennyson, G.S. & Riddell, R.H. Experimental models of inflammatory bowel disease. Gastroenterology 109, 1344-1367 (1995).
2. Kiesler, P., Fuss, I.J. & Strober, W. Experimental Models of Inflammatory Bowel Diseases. Cell Mol Gastroenterol Hepatol 1, 154-170 (2015).
3. Mourad, F.H., Yau, Y., Wasinger, V.C. & Leong, R.W. Proteomics in Inflammatory Bowel Disease: Approach Using Animal Models. Dig Dis Sci 62, 2266-2276 (2017).
Establishment of Inflammatory Bowel Disease Mouse Model
Experimental Animals：C57BL/6N, 7-10 weeks old, female
Detection Indicator：Body Weight, Colon Weight, Colon length
Modeling reagent：TNBS (trinitrobenzene sulfonate)
Efficacy Validation on IBD(wild-type C57BL/6) Mouse Model for CD4-GK1.5-mlgG2a
Effects of CD4-GK1.5-mlgG2a on TNBS-induced acute intestinal inflammation. Animals presensitizated with TNBS solution to the shaved skin area on day 0, and then received TNBS intrarectal administration on day 7. Body weight were recoded every day. CD4-GK1.5-mIgG2a (3, 10 mg/kg, i.p.) were injected on day 6. Mice were sacrificed on day 10 and colon weight (A) and length (B) were record, colon weight，body ratio were calculated (D-F).
Establishment of IBD Mouse Model
Percentage of initial body weight, clinical score and stool consistency of IBD mouse model were recoded every day.
Gross Sampling and Histologic Assessment of colon of IBD model
Representative pictures of gross anatomy and ratio of colonic weight and length of IBD mice. Values are expressed as mean ± SEM. **p<0.01.
Representative pictures of intestinal pathological tissue section of CD4+CD45RBhigh T cell -induced IBD model.
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