三氧化二砷对类风湿关节炎滑膜细胞的影响

Effect of arsenic trioxide on rheumatoid synoviocytes

目的类风湿关节炎(rheumatoid arthritis,RA)的滑膜B型细胞(成纤维细胞样细胞)是增殖滑膜的增殖细胞,表达c-myc基因。本项实验研究三氧化二砷(arsenic trioxide,As2O3)是否影响体外培养的RA滑膜B型细胞的增殖及c-myc基因表达。方法分离、培养RA滑膜B型细胞;用含As2O3浓度分别为2μmol/L和5μmol/L的培养液,分别作用于培养细胞24h和48h;采用流式细胞仪测定细胞死亡情况;采用流式细胞仪测定c-myc蛋白水平。结果2μmol/L As2O3和5μmol/L As2O3作用于RA滑膜B型细胞24h均可使死亡细胞百分率增加,2μmol/L As2O3致细胞死亡率高于5μmol/L As2O3致细胞死亡率,而48h死亡细胞百分率较24h减少,;5μmol/L As2O3作用于细胞48h促进RA滑膜B型细胞增殖,并使c-myc蛋白水平增高。结论As2O3依据作用时间和浓度的不同既可诱导RA滑膜B型细胞死亡,又可促进RA滑膜B型细胞增殖,并上调c-myc基因表达。

Objective Type B synovioeytes （fibroblast-Like synoviocytes）of rheumatoid arthritis are the proliferative cells in proliferative synovium. This study investigated if arsenic trioxide（As2O3 ） can reduce rheumatoid synoviocytes and change c-myc gene expression. Methods Type B synoviocytes of a patient with rheumatoid arthritis were separated and cultured. Synoviocytes were treated by 2μmol/L and 5μmol/L As2O3 medium for 24 h and 48 h. Death cells were an- alyzed by flow cytometry. Levels of c myc protein were measured by flow cytometry. Results After treatment for 24 h by 2μmol/L and 5μmol/L As2O3, cells death rates in both groups increased. The death rate of cells treated by 2μmol/L As2O3 was higher than that by 5μmol/L As2O3, The cells death rates on 48 h were lower than that on 24 h. 5μmol/L As2O3 promoted synoviocytes proliferation on 48 h and up-regulated c-myc expression. Conclusion By concentration and administration duration, As2O3 can induce rheumatoid synovial type B cells death as well as promote the cells proliferation and up-regulate c-myc expression.