银杏素促进成纤维样滑膜细胞中TRAF3蛋白的表达缓解类风湿关节炎  

Ginkgetin alleviates rheumatoid arthritis by promoting TRAF3 protein expression in fibroblast-like synoviocytes

作　　者：吕昌伟 张静涛 郗海涛 强毅 张乾 Lü Changwei;ZHANG Jingtao;XI Haitao;QIANG Yi;ZHANG Qian(Affiliated Hospital of Northwest University/Xi’an Third Hospital Orthopaedics, Xi’an 710018, China)

机构地区：[1]西北大学附属医院/西安市第三医院骨科,陕西西安710018

出　　处：《中国骨质疏松杂志》2022年第2期178-184,共7页Chinese Journal of Osteoporosis

基　　金：陕西省重点研发计划项目-社会发展领域(2019SF-194)。

摘　　要：目的探究银杏素(ginkgetin)治疗类风湿关节炎(rheumatoid arthritis,RA)的潜在机制。方法通过TNF-α刺激成纤维样滑膜MH7A细胞建立炎性细胞模型,用银杏素单独处理或分别与TNF受体相关因子3(tumor necrosis factor receptor-associated factor 3,TRAF3)的小干扰RNA(si-TRAF3)和p38激动剂茴香霉素共同处理,检测细胞增殖、凋亡、炎症因子白介素(interleukin,IL)-6、IL-1β分泌、TRAF3蛋白表达和p38蛋白磷酸化水平。此外,建立CIA大鼠模型并给予口服银杏素,评估大鼠关节炎指数,足爪肿胀度和滑膜组织病理学,检测滑膜组织TRAF3表达以及TNF-α、IL-6和IL-1β水平。结果银杏素上调了TRAF3表达,抑制了MH7A细胞增殖及炎症因子分泌,促进凋亡,阻断p38 MAPK信号通路。而转染si-TRAF3或添加茴香霉素处理,可逆转银杏素对MH7A细胞增殖、凋亡和炎症因子分泌以及p38 MAPK信号通路的调节作用。此外,银杏素治疗降低了CIA大鼠关节炎指数、足爪肿胀度以及TNF-α,IL-6和IL-1β分泌。结论银杏素能够上调TRAF3表达,阻断p38 MAPK信号通路,抑制MH7A细胞增殖和炎症因子分泌,促进凋亡,进而减轻CIA大鼠的关节症状。Objective To determine the molecular mechanism of ginkgetin in the treatment of rheumatoid arthritis.MethodsThe fibroblast-like synoviocytes(MH7A)were stimulated by TNF-αto establish inflammatory cell model,which were then treated with ginkgetin alone or together with si-TRAF3 or p38 agonist anisomycin.And we measured cell proliferation,apoptosis,the secretion of inflammatory cytokines interleukin-6(IL-6)and IL-1β,and the expression of TRAF3 protein and phosphorylated p38 protein in MH7A cells.Furthermore,CIA rat model was constructed and ginkgetin was administered orally in rats.We evaluated arthritis index,paw swelling,synovial histopathology,and the expression of TRAF3 proteinand the levels of TNF-α,IL-6 and IL-1βin synovial tissues.Results Ginkgetin upregulated the expression of TRAF3,inhibited proliferation and inflammatory cytokine secretion,promoted apoptosis and blocked the p38 MAPK signaling pathway in MH7A cells.However,treatment with si-TRAF3 or anisomycin reversed the regulatory effects of ginkgetin on proliferation,apoptosis,inflammatory cytokine secretion and the p38 MAPK signaling pathway in MH7A cells.Moreover,ginkgolin treatment decreased arthritis index,paw swelling,and TNF-α,IL-6 and IL-1βsecretion in CIA rats.Conclusion Ginkgetin upregulated TRAF3 expression,blocked p38 MAPK signaling pathway,inhibited MH7A cell proliferation and inflammatory cytokine secretion,promoted cell apoptosis,and further alleviated RA in CIA rats.

关 键 词：银杏素 TRAF3 类风湿关节炎 成纤维样滑膜细胞 CIA大鼠 p38 MAPK信号通路 

分 类 号：R285.5[医药卫生—中药学]