目的 构建脾虚湿阻型银屑病小鼠模型，并从多维度、多方向评价该模型，以期为中医药治疗脾虚湿阻型银屑提供研究支持。方法 采用高脂饮食喂养建立脾虚湿阻证小鼠模型，外涂咪喹莫特乳膏建立银屑病小鼠模型，并二者结合构建病证结合小鼠模型。比较体质量、进食量和饮水量，评价脾虚湿阻证候指征。比较皮损面积、PASI 评分、经皮水分丢失值、HE 染色下皮肤病理学改变评价银屑病严重程度。流式细胞术检测各类细胞表达情况，评价炎症程度。观察脂肪指数、肝脏 HE 染色下肝脏病理学变化、RT-qPCR 法检测肝脏和附睾脂肪的相关因子 mRNA 表达水平、Western Blot 法检测皮肤 ABCA1 蛋白表达水平，评价脂代谢紊乱情况。结果 与寻常型银屑病组小鼠比较，脾虚湿阻型银屑病组小鼠体质量升高 （P＜0.001） ，进食量下降 （P＜0.005） ，出现毛发油腻，精神萎靡等脾虚湿阻证候指征；经皮水分丢失值升高 （P＜0.001） ，PASI 评分增加 （P＜0.001） ，皮肤 HE 染色病理结果提示表皮棘层肥厚、杵状增生等银屑病样表现；CD11bhighLy6G+中性粒细胞、CD11binLy6Chigh单核细胞、CD11binCD11chigh经典树突细胞、F4/80-CD11c+树突状细胞表达上升 （P＜0.001） ；肝脏HE 染色病理结果提示细胞空泡样变性，且皮下白色脂肪指数和附睾脂肪指数上升 （P＜0.005） ；肝脏 FABP4、CD36 mRNA 水平升高（P＜0.005，P＜0.001）；附睾脂肪 ABCA1 和 PPARγ mRNA 水平下降（P＜0.05，P＜0.01） ，皮肤 ABCA1 蛋白水平升高 （P＞0.05） 。结论 脾虚湿阻型银屑病小鼠模型可作为可靠的病证结合动物模型，为进一步探讨中医药治疗脾虚湿阻型银屑病提供参考。

Objective To construct a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern and evaluate the model from multiple dimensions and directions，expects to provide research support for the study of traditional Chinese medicine （TCM） treatment of psoriasis with spleen deficiency and dampness obstruction pattern. Methods A mouse model of spleen deficiency and dampness obstruction pattern was established by feeding a high-fat diet，a mouse model of psoriasis vulgaris was established by externally applying imiquimod ointment，and a mouse model of psoriasis with spleen deficiency and dampness obstruction pattern was constructed by combining the above two models. Indications of spleen deficiency and dampness obstruction pattern were evaluated by comparing the body mass，food intake and water intake of mice in each group. The severity of psoriasis in mice was evaluated by comparing the area of skin lesions，PASI score，the value of transdermal water loss （TEWL），and histopathological morphological changes of skin under HE staining in each group. Flow cytometry was used to detect the expression in various cell types to evaluate the degree of inflammatory response of psoriasis in mice. Observation of adiposity index， changes in the histopathological morphology of liver tissue under HE staining，changes in the mRNA expression levels of related factors in liver tissue and adipose tissue of epididymis of mice detected by RT-qPCR，and changes of ABCA1 protein expression level of skin detected by Western Blot were used to evaluate the lipid metabolism disorders in mice. Results Compared with the mice in the psoriasis vulgaris model group， the mice in the model of psoriasis with pattern of spleen deficiency and dampness obstruction had significantly higher body mass （P＜0.001），significantly lower food intake （P＜0.005），and the symptoms of pattern of spleen deficiency and dampness obstruction such as greasy fur mental fatigue etc. appeared. The TWELwere significantly increased（P＜0.001），and the PASI scores also significantly increased（P＜0.001）. HE results were found psoriasis-like manifestations including hypertrophy of the spinous layer and clubbed hyperplasia. The expression of CD11bhighLy6G+ neutrophil subpopulation，CD11binLy6Chigh monocyte subpopulation，CD11binCD11chigh classical dendritic cell subpopulation，F4/80-CD11c+ dendritic cell subpopulation was significantly increased （P＜0.001）. HE staining suggested that the cellular morphology of liver showed obvious vacuolated degeneration，and the index of subcutaneous white adiposity and epididymal adiposity index were both significantly increased （P＜0.005）. The mRNA levels of FABP4 and CD36 in liver tissue were significantly elevated（P＜0.005，P＜0.001），while the mRNA expression levels of ABCA1 and PPARγ in epididymal fat tissue were decreased （P＜0.05，P＜0.01）. ABCA1 protein level in skin increased （P＞0.05）. Conclusion The mouse model of psoriasis with spleen deficiency and dampness obstruction pattern can be used as a reliable animal model for combining disease and pattern，which can provide a reference for further exploration of TCM in the treatment of psoriasis with spleen deficiency and dampness obstruction pattern.

R285.5

国家自然科学基金项目 （82374313） ；广东省科技计划项目 （2020B1111100006，2023B1212060063）；广州市科技计划项目 （202201020332）；省部共建中医湿证国家重点实验室重点项目 （SZ2021ZZ29）；广东省中医院拔尖人才科研专项 （BJ2022KY05)。