加味牛蒡子汤促进自发性类风湿关节炎小鼠淋巴管生成抑制炎症免疫反应  

Jia-Wei-Niu-Bang-Zi-Tang promotes lymphangiogenesis in TNF-αtransgenic mice and alleviates rheumatoid arthritis

作　　者：方叶 王晓赟 尤佳锋[1] 梁倩倩[2,3,4] 郑为超 FANG Ye;WANG Xiao-yun;YOU Jia-feng;LIANG Qian-qian;ZHENG Wei-chao(Medical Faculty,Anhui University of Science and Technology,Huainan Anhui 232001,China;Longhua Hospital Affiliated to Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;Institute of Spine Diseases,Shanghai Institute of Traditional Chinese Medicine,Shanghai 200032,China;Key Lab of Ministry of Education(Theory and Therapy of Muscles and Bones),Shanghai 200032,China)

机构地区：[1]安徽理工大学医学院,安徽淮南232001 [2]上海中医药大学附属龙华医院,上海200032 [3]上海市中医药研究院脊柱病研究所,上海200032 [4]筋骨理论与治法教育部重点实验室,上海200032

出　　处：《中国药理学通报》2021年第10期1469-1474,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81822050,81904227);上海市卫生健康委资助上海市医学领军人才(No 2019LJ02)。

摘　　要：目的探究中药复方加味牛蒡子汤(JWNBZT)对自发性类风湿关节炎模型小鼠踝关节周围淋巴管生成和分布及炎症免疫反应变化的影响。方法将3月龄左右的10只TNF-α转基因(TNF-Tg)小鼠随机均分成两组,另取5只同窝野生型小鼠作空白对照,并分别给予加味牛蒡子汤和等量生理盐水灌胃,连续给药12周。阿尔新蓝-苏木精形态学染色(ABOG染色),免疫组化及免疫荧光染色,观察踝关节炎症浸润和形态结构的改变,以及周围淋巴管新生和分布的变化。结果加味牛蒡子汤治疗后,TNF-Tg小鼠的炎症明显改善,软骨侵蚀减轻,骨量增加(P<0.01);炎症性巨噬细胞明显减少,且相关炎症因子TNF-α、iNOS表达水平下调(P<0.01);踝关节周围组织内LYVE-1+/Podoplanin+的毛细淋巴管增多,分布较广(P<0.05),毛细淋巴管的成熟和汇集增加(P<0.01)。结论加味牛蒡子汤可促进踝关节周围淋巴管增生,减轻TNF-Tg小鼠类风湿关节炎症。Aim To investigate the effect of Chinese traditional medicine Jia-Wei-Niu-Bang-Zi-Tang(JWNBZT)on the formation and distribution of lymphatic vessels around the ankle and the changes of inflammatory immune response in mouse model of spontaneous rheumatoid arthritis.Methods Ten TNF-αtransgenic(TNF-Tg)mice aged about three months were randomly divided into two groups,and another five wild type mice with the same litter were taken as blank control.The mice were given Jia-Wei-Niu-Bang-Zi-Tang and the same amount of normal saline by intragastric administration for 12 weeks.Alxin blue-hematoxylin morphological staining(ABOG staining),immunohistochemistry and immunofluorescence staining were used to observe the inflammatory infiltration and the morphological changes of the ankle joint,as well as changes in peripheral lymphangiogenesis and distribution.Results After Jia-Wei-Niu-Bang-Zi-Tang treatment,inflammation of TNF-Tg mice was significantly improved,cartilage erosion was alleviated,and bone mass increased(P<0.01).The number of inflammatory macrophages significantly decreased,and the expression levels of TNF-αand iNOS were down-regulated(P<0.01).Lymphatic capillaries of LYVE-1+/Podoplanin+increased and were widely distributed in the tissues around the ankle(P<0.05),and the maturation and collection of lymphatic capillaries increased(P<0.01).Conclusion JWNBZT can promote lymphatic hype rplasia around ankle joint and alleviate rheumatoid arthritis in TNF-Tg mice.

关 键 词：类风湿关节炎 加味牛蒡子汤 TNF-α 淋巴管 M1巨噬细胞 免疫荧光 

分 类 号：R-332[医药卫生] R282.71