目的 比较葡聚糖硫酸钠（DSS）诱导的溃疡性结肠炎（UC）小鼠疾病模型及高脂饮食诱导的湿热蕴肠证小 鼠模型，及两者病证结合模型，探讨建立湿热蕴肠型溃疡性结肠炎小鼠模型的可行性。方法 高脂饲料喂养小 鼠建立湿热蕴肠证模型，DSS 诱导溃疡性结肠炎模型，高脂饲料结合 DSS 建立湿热蕴肠型溃疡性结肠炎病证 结合小鼠模型。比较各组动物证候表现和血清生化指标，进行湿热症状评分；比较体质量、结肠长度、疾病活 动指数（DAI）评分及脾脏质量，评价溃疡性结肠炎的严重程度；结肠苏木精-伊红染色（HE）评估病理情况；流 式细胞术检测结肠中 M1/M2 型巨噬细胞的比例，联酶免疫吸附实验（ELISA）检测结肠炎性因子（TNF-α、IL-1β） 表达，评价炎症程度。结果 （1）湿热蕴肠证模型建立期间，与正常组比较，湿热蕴肠证组体质量明显升高 （P＜0.01），出现毛发油腻污秽、弓背蜷缩、肛门灼热、便稀尿少等湿热指征；结合 DSS 诱导后，与正常组比 较，溃疡性结肠炎组和湿热蕴肠型溃疡性结肠炎组体质量和结肠长度都明显减少（P＜0.01，P＜0.001），且湿 热证指征明显，表明湿热蕴肠型溃疡性结肠炎模型建立成功。（2）与正常组比较，溃疡性结肠炎组小鼠体质量明 显降低（P＜0.01），结肠缩短、脾脏系数升高（P＜0.01），DAI 指数显著升高（P＜0.001）；与溃疡性结肠炎组比 较，湿热蕴肠型溃疡性结肠炎组小鼠体质量降低（P＜0.01），结肠缩短、脾脏系数升高（P＜0.05），结肠组织病 理学评分和 DAI 指数显著升高（P＜0.05，P＜0.01）。（3）与正常组比较，溃疡性结肠炎组小鼠结肠组织 M1/M2 型巨噬细胞比例明显升高（P＜0.05），炎性因子表达明显升高（P＜0.05，P＜0.01）；与溃疡性结肠炎组小鼠相 比，湿热蕴肠型溃疡性结肠炎组 M1 型巨噬细胞比例和炎性因子表达明显升高（P＜0.05）。结论 高脂饮食结 合 DSS 诱导的湿热型溃疡性结肠炎小鼠模型既有湿热蕴肠证的中医表现，也有溃疡性结肠炎的临床特征，可 成为有效的病证结合动物模型，为今后湿热蕴肠型溃疡性结肠炎病理药理机制研究、中医药药效评价等提供模 型参考。

Objective To explore the feasibility of establishing a mouse model with ulcerative colitis （UC） of dampheat accumulation in the intestines syndrome type by comparing the disease model of UC induced by Dextran Sulfate Sodium （DSS），the damp-heat accumulation in the intestines syndrome type of UC mouse model induced by a high-fat diet， and their combined model. Methods A damp-heat accumulation in the intestines syndrome model was established by feeding mice a high-fat diet，and a UC model was induced by DSS. A combined model of damp-heat accumulation in the intestines type of UC was established by combining a high-fat diet with DSS. The syndrome manifestations and serum biochemical indicators of each group were compared，and damp-heat symptom scores were assessed. Body mass，colon length，disease activity index （DAI） scores，and spleen mass were compared to evaluate the severity of UC. Hematoxylin-eosin （HE） staining of the colon was performed to assess pathological changes. The proportion of M1/M2 macrophages in the colon was detected by flow cytometry， and the expression of inflammatory factors （TNF-α，IL-1β） in the colon was measured by enzyme-linked immunosorbent assay （ELISA） to evaluate the degree of inflammation. Results （1） During the establishment of the damp-heat accumulation in the intestines syndrome model， compared with the normal group， the body mass of the damp-heat accumulation in the intestines group significantly increased （P＜0.01），with manifestations such as greasy and dirty fur，hunched posture，anal burning，loose stools，and reduced urine output. After DSS induction，compared with the normal group，the body mass and colon length of the UC group and the damp-heat accumulation in the intestines of UC group significantly decreased （P＜0.01， P＜0.001）， and damp-heat accumulation in the intestines syndrome manifestations were evident， indicating the successful establishment of the damp-heat accumulation in the intestine type of UC model. （2）Compared with the normal group，the UC group showed a significant decrease in body mass （P＜0.01），shortened colon length，increased spleen index （P＜0.01），and significantly elevated DAI scores （P＜0.001）. Compared with the UC group，the damp-heat accumulation in the intestines type of UC group exhibited a further decrease in body mass （P＜0.01）， shortened colon length， increased spleen index （P＜0.05）， and significantly higher colon histopathological scores and DAI scores （P＜0.05，P＜0.01）. （3） Compared with the normal group，the UC group showed a significant increase in the M1/M2 macrophage ratio in colon tissues （P＜0.05） and elevated expression of inflammatory factors （P＜0.05，P＜0.01）. Compared with the UC group，the damp-heat accumulation in the intestine tpye of UC group exhibited a further increase in the proportion of M1 macrophages and inflammatory factor expression （P＜0.05）. Conclusion The high-fat diet combined with DSS-induced damp-heat accumulation in the intestine type of UC mouse model exhibits both traditional Chinese medicine manifestations of damp-heat accumulation in the intestines and clinical features of UC，making it an effective disease-syndrome combined animal model. This model provides a reference for future research on the pathological and pharmacological mechanisms of damp-heat accumulation in the intestine type of UC and the evaluation of traditional Chinese medicine efficacy.

R285.5

江西省“科技+中医药”联合计划项目（2023KZI01001）；江西中医药大学中西医结合一级学科（江西省双一流学科zxyylxk20220103）