新雷公藤衍生物雷藤舒对类风湿关节炎滑膜细胞基因表达的影响  

Effects of (5R)-5-Hydroxytriptolide(LLDT-8) on Gene Expressions in Fibroblast-like Synoviocytes of Rheumatoid Arthritis

作　　者：刘佳 童萍 何东仪 

机构地区：[1]上海光华中西医结合医院风湿病科,上海200052

出　　处：《上海中医药大学学报》2017年第6期70-75,共6页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：国家自然科学基金资助项目(81273979);上海市卫计委科研基金资助项目(201640192);上海市进一步加快中医药事业发展三年行动计划项目(ZY3-LCPT-1);上海市长宁区科委科研基金资助项目(CNKW2016Y08)

摘　　要：目的:研究新雷公藤衍生物雷藤舒[(5R)-5-hydroxytriptolide,LLDT-8]对肿瘤坏死因子(TNF)-α联合白介素(IL)-17诱导的类风湿关节炎(rheumatoid arthritis,RA)患者成纤维样滑膜细胞(fibroblast-like synoviocytes,FLS)信号通路的调节作用。方法:体外培养RA FLS,根据干预措施不同分为实验组和对照组。实验组加入LLDT-8+DMEM培养液,对照组加入等容量DMEM培养液;培养24 h后,实验组和对照组同时加入含TNF-α、IL-17的DMEM培养液;刺激12 h后,收集细胞,分离获取总RNA。采用Aglient基因表达谱芯片检测RA FLS基因表达的变化,利用KEGG数据库分析LLDT-8对RA FLS Pathway的影响。结果:(1)LLDT-8干预TNF-α联合IL-17诱导RA FLS后差异表达基因共408条,其中上调基因119条,下调基因289条。(2)LLDT-8能调控TNF-α联合IL-17诱导的RA FLS的细胞因子受体通路、趋化因子信号转导通路、Toll样受体通路、TNF信号通路、核因子-κB(NF-κB)信号通路、JAK-STAT信号通路等多条RA相关通路。结论:LLDT-8可能通过双向调节细胞因子受体通路、趋化因子信号转导通路,下调Toll样受体、NF-κB、JAK-STAT等信号通路达到抗RA作用,为进一步临床运用提供实验依据。Objective： To study the regulatory effects of （5 R）-5-hydroxytriptolide （LLDT-8） on the signaling pathways of fibroblast-like synovioeytes （FLS） in patients with rheumatoid arthritis （RA） induced by TNF-α and IL-17. Methods： RA FLS was cultured in vitro and divided into the experiment group and control group according to the different interventions. The experiment group was treated with LLDT-8 plus DMEM culture medium and the control group was treated with DMEM culture medium at equal volume. After incubation for 24 hours, both groups were stimulated by DMEM containing TNF-α and IL-17 for 12 hours. Then the cells were collected and the total RNA was isolated and obtained. The changes on gene expressions of RA FLS were detected by Aglient gene expression profile chip. The effects of LLDT-8 on the RA FLS pathways were analyzed by KEGG database. Results：①After the intervention of LLDT-8 on RA FLS induced by TNF-α and IL-17,408 differential expression genes were found between the control group and experiment group, in which 119 genes were up-regulated and 289 genes were down-regulated. ②LLDT-8 could regulate multiple signaling pathways related to RA in RA FLS induced by TNF-α and IL- 17, such as cytokine-cytokine receptor interaction, ehemokine signaling pathway, Toll-like receptor signaling pathway, TNF signaling pathway, NF-κB signaling pathway, JAK-STAT signaling pathway and so on. Condusion： LLDT-8 shows the bidirectional regulatory effects on the cytokine-cytokine receptor interaction and chemokine signaling pathway, and down- regulatory effects on the Toll-like receptor signaling pathway, NF-κB signaling pathway and JAK-STAT signaling pathway to counteract RA, which provide the experimental evidence for further clinical application.

关 键 词：雷藤舒 类风湿关节炎 成纤维样滑膜细胞 基因芯片 

分 类 号：R285[医药卫生—中药学]