来氟米特代谢物teriflunomide调节NFATc1基因抑制破骨细胞分化作用研究  

Osteoclast Differentiation Inhibited by Active Metabolite of Leflunomide through Regulating NFATc1 Expression

作　　者：姚瑶[1] 丁从珠[2] 葛卫红[1] 

机构地区：[1]南京大学医学院附属鼓楼医院药学部,南京210008 [2]南京大学医学院附属鼓楼医院风湿免疫科,南京210008

出　　处：《药学与临床研究》2012年第4期285-288,共4页Pharmaceutical and Clinical Research

基　　金：江苏省六大人才高峰计划项目(2010-057);南京市卫生局医学科技发展项目(YKK11101);南京市卫生局医学科技发展重点项目(ZKX08022)

摘　　要：目的:探讨来氟米特代谢活性物质teriflunomide对人外周血单核细胞向破骨细胞分化的抑制作用及其机制。方法:梯度离心法分离外周血单核细胞,MTT法测定teriflunomide对外周血单核细胞的毒性作用,TRAP染色鉴定其对外周血单核细胞向破骨细胞分化的抑制作用,RT-PCR法测定teriflunomide对外周血单核细胞NFATc1基因的表达影响。结果:Teriflunomide对外周血单核细胞的增殖无显著影响,能够显著抑制破骨细胞的分化成熟,且能够有效抑制NFATc1基因的表达。结论:Teriflunomide能够通过抑制破骨细胞分化启动基因NFATc1的表达,有效抑制外周血单核细胞向成熟破骨细胞的分化,且对正常单核细胞无毒性作用。Objective： To investigate the inhibition of peripheral blood mononuclear cells （PBMC） differentiation by teriflunomide, the active metabolite of leflunomide, and its mechanism. Method： PBMC were isolated from healthy peripheral blood. Cell proliferation was detected through MTT assay when interfered with different concentrations of teriflunomide. Osteoelast eell （OC） differentiation was observed through TRAP dyeing. NFATel expression was indicated through RT-PCR assay. Result： The MTT results indicated that cell proliferation were not affected in any eoneentration group of teriflunomide （P〉0.05）. The mature OC number in the 1000 μmol·L^-1 teriflunomide group was obviously less than that in the control group on d 16 （P〈0.05）. The RT-PCR results indieated that the NFATel relative expression in OC was decreased to 0.72 with the 24 h treatment of teriflunomide at 1000μmol·L^-1. Conclusion： Teriflunomide suppl＇essed the differentiation from PBMC to OC by redueing NFATcl expression, moreover, there was no toxic effect on KEY WORDS normal PBMC Leflunomide; Peripheral blood mononuelear cell; Osteoclasts

关 键 词：来氟米特 外周血单核细胞 破骨细胞 

分 类 号：R971.1[医药卫生—药品] R979.5[医药卫生—药学]