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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 被引量:23

Effects of methotrexate on cell proliferation and cell cycle of synovial fibroblasts in patients with rheumatoid arthritis
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摘要 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.方法应用四唑氮化合物(MTS)/黄嘌呤氧化酶(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 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 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. Objective To investigate the effect of methotrexate(MTX) on cell proliferation and cell cycle of synovial fibroblasts in patients with rheumatoid arthritis(RA),and evaluate the mechanisms of MTX in treating RA.Methods The level of cell proliferation and cell cycle of synovial fibroblasts treated and not-treated with MTX in patients with rheumatoid arthritis were measured by MTS/PMS cell proliferation assay and fluorescence-activated cell sorting(FACS) method.Results Level of proliferation of MTX-treated (0.2 to 2 μmol/L) synovial fibroblasts in patients with RA was significantly decreased compared with corresponding not-treated group (P<0.05) since the fourth day.FACS assay showed the rate of MTX-treated (0.2 to 2 μmol/L) synovial fibroblasts in patients with RA in G1 phase as significantly increased than not-treaded group (P<0.05) in the fifth or eighth day,as well as the rate of synovial fibroblasts in S phase and G2 phase(P<0.05).MTX inhibited proliferation of synovial fibroblasts in a dose-dependent manner.Conclusion The findings suggest that MTX inhibites the proliferation and proliferation-dependent processes of synovial fibroblasts in patients with RA.
出处 《中华风湿病学杂志》 CAS CSCD 2004年第4期223-226,共4页 Chinese Journal of Rheumatology
基金 湖北省科学技术委员会科研基金资助项目(2002AA-301C47)
关键词 甲氨蝶呤 类风湿关节炎 滑膜细胞增生 细胞周期 流式细胞术 测定 Arthritis,rheumatoid Synovial membrane Cell Hyperplasia Periodicity Drug evaluation
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参考文献5

  • 1Fairbanks LD,Ckemann KR,Qiu Y,et al. Methotrexate inhibits the first committed step of purine biosynthesis in mitogen-stimulated human T-lymphocytes:a metabolic basis for efficacy in rheumatoid arthritis?Biochem J,1999,342:143-152.
  • 2Quemeneur L,Gerland LM,Flacher M,et al.Differential control of cell cycle,proliferation,and survival of primary T lymphocytes by purine and pyrimidine nucleotides. J Immunol,2003,170:4986-4995.
  • 3Sgambato A,Camerini A,Pani G,et al. Increased expression of cyclin E is associated with an increased resistance to doxorubicin in rat fibroblasts. Br J Cancer,2003,88:1956-1962.
  • 4Perlman H,Bradley K,Liu H,et al. IL-6 and matrix metalloproteinase-1 are regulated by the cyclin-dependent kinase inhibitor p21 in synovial fibroblasrs.J Immunol,2003,170:838-845.
  • 5Genestier L,Paillot R,Fournel S,et al. Immunosuppressive properties of methotrexate:apoptosis and clonal deletion of activated peripheral T cells.J Clin Invest, 1998,102:322-328.

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