来源：风湿病与关节炎,2023,12（1）:1-5,18.

基于脾虚湿阻研究佐剂性关节炎大鼠模型炎性因子、钠钾ATP酶及病理组织学变化（基础研究）

刘德芳，张耀雷，刘碧莹，李　莞，刘　涛，郭明阳，晏　姣

　　【摘　要】目的：建立基于脾虚湿阻环境下的佐剂性关节炎（AA）大鼠模型，观测其炎性关节的炎性因子、脾脏钠钾ATP酶（Na⁺，K⁺-ATPase）表达及关节的病理组织学变化。方法：将30只Wistar大鼠按照随机数字表法分为模型组、AA对照组、空白对照组，每组10只。模型组在脾虚湿阻环境下复制AA大鼠模型，AA对照组在常温常湿下复制AA模型，空白对照组给予常温常湿环境喂养。28 d后，观察大鼠的进食量、精神状态、毛发、关节肿胀度、活动情况，以及关节的病理组织学；检测血常规，炎性关节的白细胞介素-6（IL-6）、肿瘤坏死因子-α（TNF-α）、血管内皮生长因子（VEGF）表达及脾脏的Na⁺，K⁺-ATPase活性。结果：与对照组比较，模型组大鼠精神萎靡，进食量减少，部分大鼠腹泻，毛发失去光泽，关节肿胀，部分足底部溃烂，活动迟缓或跛行；模型组大鼠关节的病理组织学表现为滑膜组织中大量淋巴细胞、浆细胞、巨噬细胞等炎性细胞浸润，滑膜增生呈多层化，纤维血管翳形成。血小板计数、中性粒细胞比率和单核细胞比率明显升高（P < 0.05），淋巴细胞比率明显降低（P < 0.05），IL-6、TNF-α、VEGF表达明显升高（P < 0.05），Na⁺，K⁺-ATPase活性减退（P < 0.05）。结论：模型组大鼠表现出关节明显肿胀，足底部溃烂，饮食量减少，大便溏泻，Na⁺，K⁺-ATPase活性减退，类同于中医痹病脾虚湿阻的范畴，血细胞计数、比率和IL-6、TNF-α、VEGF等异常表达，以及关节的病理组织学表现与类风湿关节炎患者表现一致。

　　【关键词】　类风湿关节炎；佐剂性关节炎；动物模型；炎性因子；钠钾ATP酶；大鼠

Study on Inflammatory Factors,Na⁺,K⁺-ATPase and Histopathological Changes of Adjuvant Arthritis Rat Model Based on Spleen Deficiency and Dampness Obstruction

LIU De-fang,ZHANG Yao-lei,LIU Bi-ying,LI Wan,LIU Tao,GUO Ming-yang,YAN Jiao

　　【ABSTRACT】Objective:To establish rat models of adjuvant arthritis（AA）based on the environment of spleen deficiency and dampness obstruction,and observe the inflammatory factors of its inflammatory joints,the expression of sodium potassium ATPase（Na⁺,K⁺-ATPase）in the spleen and the pathological changes of the joints.Methods:Thirty Wistar rats were randomly divided into a model group,an AA control group and a blank control group,with 10 rats in each group.The model group reproduced the AA rat model in the environment of spleen deficiency and dampness construction,the AA control group reproduced the AA model at normal temperature and humidity,and the blank control group was fed at normal temperature and humidity.After 28 days,observe the rats' food intake,mental state,hair,joint swelling,activity,and joint histopathology,detect blood routine,IL-6,TNF-α,expression of VEGF and activity of Na⁺,K⁺-ATPase in spleen.Results:Compared with the control group,the rats in the model group suffered from mental depression,decreased food intake,diarrhea（some rats）,loss of luster in hair,joint swelling,partial foot ulceration,slow movement or lameness;the pathological histology of the joints in the model group showed that a large number of inflammatory cells such as lymphocytes,plasma cells and macrophages infiltrated the synovial tissue,the synovial hyperplasia was stratified,and the fibrous pannus were formed.Platelet count,neutrophil ratio and monocyte ratio increased significantly（P < 0.05）,lymphocyte ratio decreased significantly（P < 0.05）,the expressions of IL-6,TNF-α and VEGF were significantly increased（P < 0.05）,and the activity of Na⁺,K⁺-ATPase was decreased（P < 0.05）.Conclusion:The rats in the model group showed obvious joint swelling,foot ulceration,reduced diet,loose stool,decreased Na⁺,K⁺-ATPase activity,similar to the category of bi disease of spleen deficiency and dampness construction in traditional Chinese medicine.The abnormal expressions of blood cell count and ratio,IL-6,TNF-α and VEGF and the histopathological manifestations of joints were consistent with those of patients with rheumatoid arthritis.

　　【Keywords】 rheumatoid arthritis;adjuvant arthritis;animal model;inflammatory factors;Na⁺,K⁺-ATPase;rats