金雀异黄素对血小板微颗粒诱导的类风湿关节炎成纤维样滑膜细胞迁移和侵袭的影响  

Effects of genistein on migration and invasion of fibroblast-like synoviocytes from rheumatoid arthritis induced by platelet-derived microparticles

作　　者：沈芹 柳桂萍 王雯雯 胡君 周玮[4] 刘家欢 王慧 沈维干[5] 张育 SHEN Qin;LIU Gui-ping;WANG Wen-wen;HU Jun;ZHOU Wei;LIU Jia-huan;WANG Hui;SHEN Wei-gan;ZHANG Yu(Dept of Rheumatology and Immunology,North Jiangsu People’s Hospital of Jiangsu Province Affiliated to Yangzhou University,Yangzhou,Jiangsu 225001,China;Dept of Rheumatology and Immunology,Taizhou People’s Hospital,Taizhou,Jiangsu 225300,China;Dept of Internal Medicine,Jiangsu Provincial General Hospital of Armed Police Force,Yangzhou,Jiangsu 225001,China;Dept of Hematology and Rheumatology,Affiliated Hospital of Yangzhou University,Yangzhou,Jiangsu 225001,China;Medical College of Yangzhou University,Yangzhou Jiangsu 225001,China)

机构地区：[1]扬州大学附属苏北人民医院风湿免疫科,江苏扬州225001 [2]泰州市人民医院风湿免疫科,江苏泰州225300 [3]江苏省武警总队医院内科,江苏扬州225001 [4]扬州大学附属医院血液风湿科,江苏扬州225001 [5]扬州大学医学院,江苏扬州225001

出　　处：《中国药理学通报》2018年第10期1408-1413,共6页Chinese Pharmacological Bulletin

基　　金：国家自然科学基金资助项目(No 81470070;81771728)

摘　　要：目的探讨金雀异黄素(genistein,Gen)对血小板微颗粒(platelet-derived microparticles,PMPs)诱导的类风湿关节炎(rheumatoid arthritis,RA)成纤维样滑膜细胞(fibroblast-like synoviocyte,FLS)迁移和侵袭的影响,并探究其可能的机制。方法应用CCK-8试剂盒检测Gen对PMPs作用后RA-FLS活力的影响;通过Transwell细胞迁移、侵袭实验,以及细胞与细胞外基质(ECM)的黏附实验,探究Gen对PMPs诱导的RA-FLS迁移、侵袭以及与ECM黏附的影响;免疫荧光染色观察Gen对PMPs作用后RA-FLS应力纤维的分布、丝状和片状伪足形成的影响;Western blot检测Gen对PMPs作用后RA-FLS中NF-κB信号通路组分的影响。结果 Gen对PMPs诱导的RA-FLS的活力无明显影响;然而,Gen可抑制PMPs诱导的RA-FLS的迁移、侵袭及黏附;同时,Gen可减少PMPs作用后RA-FLS片状伪足的形成,促进应力纤维的形成。此外,Gen能下调PMPs诱导的RA-FLS中p-IκB、pNF-κB的表达。结论Gen可抑制PMPs激活的NF-κB信号通路,影响RA-FLS的肌动蛋白细胞骨架装配,从而抑制PMPs诱导的RA-FLS与ECM的黏附、迁移和侵袭。To explore the effects of genistein(Gen)on the migration and invasion of fibroblast-like synoviocyte(FLS)from rheumatoid arthritis(RA)induced by platelet-derived microparticles(PMPs),and to reveal the underlying mechanism.Methods The CCK-8 kits were performed to examine the effects of Gen on cell viability of RA-FLS induced by PMPs.Transwell cell migration,invasion and cell-matrix adhesion assays were used to examine the effects of Gen on the migration,invasion and adhesion onto the extracellular matrix(ECM)of RA-FLS stimulated by PMPs.The immunofluorescence assay was applied to observe the effects of Gen on the distribution of stress fibers and the formation of filopodia and lamellipodia in RA-FLS after treatment with PMPs.Western blotting was performed to detect the effects of Gen on the expression of basic components of NF-κB signaling pathway in RA-FLS after treatment with PMPs.Results The effects of Gen on viability of RA-FLS induced by PMPs showed no statistical differences,whereas Gen could suppress the migration,invasion and adhesion to ECM,and decrease the lamellipodia formation and increase the stress fibre formation in RA-FLS induced by PMPs.Moreover,Gen down-regulated the levels of p-IκB and p-NF-κB in RA-FLS incubated by PMPs.Conclusions Gen can inhibit cell adhesion onto ECM,migration and invasion of RA-FLS induced by PMPs presumably via regulating NF-κB signaling pathways activated by PMPs,and thereby modulating the F-actin cytoskeleton rearrangement of RA-FLS.

关 键 词：类风湿关节炎 金雀异黄素 成纤维样滑膜细胞 细胞迁移 细胞侵袭 NF-κB 

分 类 号：R284.1[医药卫生—中药学] R322.72[医药卫生—中医学]