LEF对肾小球系膜细胞增殖及分泌细胞外基质的影响

EFFECT OF LEFLUNOMIDE ON PROLIFERATIOM AND SYNTHESIS OF EXTRACELLULAR MATRIX OF MESANGIAL CELL

目的:探讨来氟米特对转化生长因子-β_1 刺激的大鼠肾小球系膜细胞(GMCs)增殖及细胞外基质(ECM)分泌的影响。方法:体外培养大鼠肾小球系膜细胞,分正常对照组,TGF-β_1 (5 ng/mL)刺激组,TGF-β_1 +LEF(LEF浓度分别为5μmol/L、25μmol/L、50μmol/L、100μmol/L)组,培养24h、48h和72h后,MTT法观察各组肾小球系膜细胞在不同时间点的增殖情况;ELISA法测定各组培养细胞上清液中纤连蛋白的含量。结果:(1)与对照组相比,TGF-β_1 可刺激系膜细胞增殖,不同浓度的LEF均可以抑制TGF-β_1 刺激的系膜细胞增殖(P<0.05),48h后抑制作用稳定。(2)TGF-β_1 刺激组细胞上清液中纤连蛋白含量明显高于对照组(P<0.05),不同浓度的LEF组纤连蛋白含量明显低于TGF-β_1 组(P<0.05)。结论:来氟米特可以抑制TGF-β_1 刺激的肾小球系膜细胞的增殖,减少细胞外基质的分泌,为其治疗慢性肾脏病提供理论依据。

Objective：This study is to discuss the effects of Leflunomide on proliferation and synthesis of extracellular matrix in rat renal mesangial cells stimulated with transforming growth factor-betal.Methods：GMCs were cultured in vitro.Experiment groups：Normal control group,TGF-β1（5 ng/mL）-stimulated group,TGF-β1 plus LEF（concentrations：5μmol/L,25μmol/L,50μmol/L,100μmol/L）group.Inhibitions of proliferations of GMCs were analyzed by MTT assay at 24h,48h and 72h.The expressions of fibronectin were analyzed by enzyme linked immunosorbent assay（ELISA）.Results：（1）Comparison with the normal control group,the TGF-β1 can stimulate the proliferation of GMCs,and all concentrations of LEF could inhibit the proliferation of GMCs which is stimulated by TGF-β1（P〈0.05）.Te effect reached the maxlmum at 48h.（2）With the stimulation of TGF-β1,the expression of fibronectin were markly increased（P〈0.05）.It could decreased by the treatment of different concentrations LEF（P〈0.05）.Conclusion：LEF could inhibit the proliferation of GMCs by stimulated with TGF-β1 and synthesis of extracellular matrix.It provides the foundation for treatmenting chronic kidney disease.