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

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.