甲氨蝶呤对类风湿关节炎滑膜细胞增生及细胞周期的影响

目的研究甲氨蝶呤(MTX)对类风湿关节炎(RA)滑膜细胞增生及细胞周期的影响,揭示MTX治疗RA的机制。方法应用MTS/PMS比色法和流式细胞术分别测定MTX处理和未处理RA患者滑膜细胞的细胞增生水平和细胞周期。结果加入不同浓度MTX(0.2~2.0 μmol/L),RA患者滑膜细胞接种后第4天起增生水平均显著低于未处理的RA患者滑膜细胞(P<0.05);细胞周期分析显示加入不同浓度MTX(0.2~2.0 μmol/L)后第5、8天,RA患者滑膜细胞停留在G1期的比例要比未处理的RA患者滑膜细胞明显增加(P< 0.05),而S、G2期的细胞比例比未处理的RA患者滑膜细胞则明显减少(P<0.05);MTX能以剂量依赖性明显抑制滑膜细胞的增生水平。结论MTX在治疗RA时,主要起到对RA患者滑膜细胞的增生及增生相关病理过程的抑制。

Effects of methotrexate (MTX) on cell proliferation and cell cycling of synovial fibroblasts in patients with rheumatoid arthritis

Objective: To investigate the effects of methotrexate (MTX) on cell proliferation and cell cycling of synovial fibroblasts in patients with rheumatoid arthritis (RA), and evaluate the mechanism of MTX in treating RA. Methods: The levels of cell liferation and cell cycle of synovial fibroblasts treated and untreated with MTX in patients with RA were measured by MTS/PMS cell lfferation assay and fluorescence-activated cell sorting (FACS) method. Results: Levels of lfferation of MTX-treated (0.2～2.0 p mol/L) synovial fibroblasts in patients with RA were significantly decreased compared with corresponding untreated group (P＜0.05) after the fourth day. FACS assay showed the rate of MTX-treated (0.2～2.0 μ mol/L) synovial fibroblasts in patients with RA in G1 phase were significantly increased than untreated group (P＜0.05) on the fifth or eighth day,the rate of synovial fibroblasts in S phase and G2 phase was significantly decreased than untreated group (P＜0.05). MTX inhibited liferation of synovial fibroblasts in a dose-dependent manner. Conclusions: The findings imply the involvement of MTX in the inhibition of synovial fibroblasts in patients with RA proliferation and proliferation-dependent processes in RA.