脏痹方治疗类风湿关节炎间质性肺疾病小鼠关节炎及肺脏并发症的疗效研究  

Efficacy of Zang Bi Formula in Treating Arthritis and Its Pulmonary Complications in Rheumatoid Arthritis Interstitial Lung Disease Mice

作　　者：杨灿 李宁[1,2,3] 李雪菲[1,2,3] 赵力 徐浩[1,2,3] 施杞 王拥军[1,2,3] 梁倩倩[1,2,3] YANG Can;LI Ning;LI Xuefei;ZHAO Li;XU Hao;SHI Qi;WANG Yongjun;LIANG Qianqian(Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Spine Institute,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Key Laboratory of Theory and Therapy of Muscles and Bones,Ministry of Education,Shanghai 200032,China)

机构地区：[1]上海中医药大学附属龙华医院,上海市200032 [2]上海中医药大学脊柱病研究所,上海市200032 [3]上海市筋骨理论与治法教育部重点实验室,200032

出　　处：《中国全科医学》2024年第24期3015-3022,共8页Chinese General Practice

基　　金：上海市卫生健康委员会中医药科研项目创新团队类项目(2022CX001);上海市医院中药制剂产业转化协同创新中心项目;上海市重中之重研究中心建设项目(2022ZZ01009)。

摘　　要：背景类风湿关节炎间质性肺疾病(RA-ILD)是类风湿关节炎(RA)常见的并发症之一,严重损害了RA患者的生活质量及生存期。脏痹方在临床多用于RA经久不愈者,但其作用机制及对RA-ILD的疗效仍不清楚。目的探讨脏痹方在RA和RA-ILD中的治疗可能性和潜在机制。方法研究时间为2022年1月—2023年3月。将14只肿瘤坏死因子α转基因(TNF-Tg)小鼠随机分为生理盐水组(Saline组)、脏痹方组(ZBF组),每组各7只。同时随机挑选7只同窝野生型小鼠作为对照组(WT组)。ZBF组给予脏痹方灌胃(1.4 g/mL,1次/d,0.2 mL/次),WT组和Saline组小鼠给予等量0.9%氯化钠溶液灌胃,连续8周。干预完成后小鼠踝关节组织分别采用苏木素-伊红(HE)染色检测炎性细胞面积,阿尔新蓝-橙黄染色检测软骨面积、骨面积占比,抗酒石酸酸性磷酸酶(TRAP)染色测量破骨细胞面积。小鼠肺组织分别采用HE染色检测炎性细胞面积占比,Masson染色检测肺纤维化情况,免疫荧光染色检测肺组织T淋巴细胞和B淋巴细胞面积占比。结果Saline组小鼠的踝关节内炎性细胞浸润明显增多,滑膜增生,关节组织被破坏。ZBF组踝关节的炎症减轻。Saline组小鼠炎性细胞面积占比高于ZBF组、WT组,ZBF组炎性细胞面积占比高于WT组(P<0.05)。Saline组小鼠踝关节距骨矢状面被严重破坏,骨侵蚀严重,ZBF组小鼠踝关节骨与软骨侵蚀明显改善,距骨矢状面轮廓逐渐清晰,骨量明显增加。Saline组软骨面积、骨面积占比低于ZBF组、WT组,ZBF组软骨面积、骨面积占比低于WT组(P<0.05)。Saline组小鼠踝关节中出现大片红色破骨细胞浸润,ZBF组小鼠破骨细胞浸润情况明显改善。ZBF组破骨细胞面积明显低于Saline组(P<0.05)。Saline组小鼠肺间质、血管和支气管周围弥漫有轻度至中度的炎性细胞浸润,中、小动脉壁增厚,肺泡间隔缩小,肺组织破坏明显;ZBF组小鼠肺间质和气管血管周围的炎性细胞减Background Rheumatoid arthritis interstitial lung disease(RA-ILD)is one of the most common complications of rheumatoid arthritis(RA)that severely impairs the quality of life and survival.Zang Bi Formula(ZBF)is mostly used in clinical practice for patients with recurrent occurrence of RA.However,its mechanism of action and efficacy in RA-ILD still remain unclear.Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD.Objective To investigate the therapeutic possibilities and potential mechanisms of the ZBF on RA and RA-ILD.Methods From January 2022 to March 2023,a total of 14 tumor necrosis factor alpha-transgenic(TNF-Tg)mice were randomly divided into Saline group and ZBF group,with 7 mice in each group.At the same time,7 wild-type(WT)mice in the same litter were randomly selected as the control group(WT group).Intragastric administration of ZBF 1.4 g/mL with 0.2 mL per time was given to mice of ZBF group once a day,and those in the WT group and Saline group were given an equal amount of normal saline via intragastric administration.After the intervention for 8 weeks,hematoxylin&eosin(H&E)staining of mouse ankle tissues was performed to observe the inflammatory cell area.Alcian blue-orange and tartrate-resistant acid phosphatase(TRAP)staining was performed to observe the cartilage area and bone area ratio,as well as the osteoclast area,respectively.The area proportion of inflammatory cells,fibrosis and T-cell/B-cell proportion in mouse lung tissues were observed by H&E staining,Masson staining and immunofluorescence staining,respectively.Results Mice in the Saline group had significantly increased inflammatory cell infiltration,synovial hyperplasia,and ankle tissue destruction.Inflammation of the ankle joint was alleviated in the ZBF group.The proportion of inflammatory cells in the Saline group was significantly higher than that of the ZBF group and WT group,which was significantly higher in the ZBF group than that of the WT group(P<0.05).Mice in the Saline gro

关 键 词：关节炎 类风湿 肺疾病 间质性 脏痹方 肿瘤坏死因子α转基因小鼠 治疗结果 

分 类 号：R593[医药卫生—内科学] R563[医药卫生—临床医学]