基于CD19^(+)B细胞调控FAK/CAPN/PI3K通路研究新风胶囊改善类风湿关节炎机制  

Mechanism of Xinfeng Capsules improving rheumatoid arthritis based on CD19^(+) B cells regulating FAK/CAPN/PI3K pathway

作　　者：万磊[1] 刘健[1] 黄传兵[1] 赵磊 谌曦[1] 范海霞[1] 葛瑶[1] 刘天阳[1] 刘磊[1] LI Zheng 朱子衡 马熙檬 李舒 WAN Lei;LIU Jian;HUANG Chuan-bing;ZHAO Lei;CHEN Xi;FAN Hai-xia;GE Yao;LIU Tian-yang;LIU Lei;LI Zheng;ZHU Zi-heng;MA Xi-meng;LI Shu(Department of Rheumatology,the First Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230031,China;Graduate School of Anhui University of Chinese Medicine,Hefei 230031,China;Department of Cancer Biology,City of Hope National Medical Center and Beckman Research Institute,California 91010,USA)

机构地区：[1]安徽中医药大学第一附属医院风湿科,安徽合肥230031 [2]安徽中医药大学研究生院,安徽合肥230031 [3]Department of Cancer Biology,City of Hope National Medical Center and Beckman Research Institute,California 91010,USA

出　　处：《中国中药杂志》2021年第14期3705-3711,共7页China Journal of Chinese Materia Medica

基　　金：国家自然科学基金面上项目(81973655);国家重点研发计划“中医药现代化研究”专项(2018YFC1705204);全国中医药创新骨干人才培训项目(国中医药人教函[2019]128号);安徽省省级质量工程教学研究项目(2018jyxm1068);安徽省名中医刘健工作室建设项目(中医药发展秘[2018]11号);安徽省第12批“115”创新团队项目(皖人才办[2019]1号);安徽中医药大学研究生创新计划基金项目(2019YJG013)。

摘　　要：观察新风胶囊对类风湿关节炎(RA)B淋巴细胞、炎性介质、FAK/CAPN/PI3K通路的影响,探讨新风胶囊改善RA临床症状的机制。观察RA患者关节及全身症状,检测实验室指标[血红蛋白(HGB)、血小板计数(PLT)、血沉(ESR)、免疫球蛋白(Ig)G、IgA、IgM、类风湿因子(RF)、抗环瓜氨酸抗体(CCP-AB)、C反应蛋白(CRP)]。采用酶联免疫吸附法检测血清白细胞介素(IL)-1β、IL-10、IL-33、趋化因子5(CCL5)、血管内皮生长因子(VEGF),流式细胞术测定外周血CD3^(-)CD19^(+)B细胞,免疫印迹法检测FAK、p-FAK、CAPN、PI3K蛋白。结果显示,新风胶囊能明显改善RA关节及全身症状,提高临床疗效。且新风胶囊能升高HGB,降低PLT、CCP-AB、CRP、ESR指标,上调IL-10表达,下调IL-1β、IL-33、CCL5、VEGF、CD3^(-)CD19^(+)B细胞、FAK、p-FAK、CAPN、PI3K表达(P<0.01)。结果表明,新风胶囊可能通过下调CD3^(-)CD19^(+)B细胞表达,调控炎性细胞因子和趋化因子平衡,抑制FAK/CAPN/PI3K通路异常激活,改善RA临床症状。To observe the effect of Xinfeng Capsules on rheumatoid arthritis(RA)B lymphocytes,inflammatory mediators,FAK/CAPN/PI3K pathway,in order to explore the mechanism of Xinfeng Capsules in improving clinical symptoms of RA.Joint and systemic symptoms of RA patients were observed,and laboratory indicators[hemoglobin(HGB),platelet count(PLT),erythrocyte sedimentation(ESR),immunoglobulin(Ig)G,IgA,IgM,rheumatoid factor(RF),anti-cyclic citrulline antibody(CCP-AB),C-reactive protein(CRP)]were detected.ELISA was used to detect serum interleukin(IL)-1β,IL-10,IL-33,chemokine 5(CCL5),and vascular endothelial growth factor(VEGF).CD3^(-)CD19^(+)B cells were measured by flow cytometry.Western blot was used to detect FAK,p-FAK,CAPN,PI3K protein.The results showed that Xinfeng Capsules could significantly alleviate RA joint and systemic symptoms and improve clinical efficacy.And Xinfeng Capsules could increase HGB,decrease PLT,CCP-AB,CRP,ESR index,upregulate IL-10 expression,and down-regulate IL-1β,IL-33,CCL5,VEGF,CD3^(-)CD19^(+)B cells,FAK,p-FAK,CAPN,PI3K expressions(P<0.01).Based on the above results,Xinfeng Capsules may reduce the expression of CD3^(-)CD19^(+),regulate the balance of inflammatory cytokines and chemokines,inhibit abnormal activation of FAK/CAPN/PI3K pathway,and improve clinical symptoms of RA.

关 键 词：类风湿关节炎 粘着斑激酶 钙蛋白酶 磷酸肌醇-3激酶 B淋巴细胞 新风胶囊 

分 类 号：R285[医药卫生—中药学]