来氟米特抑制结缔组织生长因子诱导的肾间质成纤维细胞增殖和胶原合成的研究

Leflunomide inhibit proliferation and collagen synthesis of human renal interstitial fibroblasts induced by CTGF

目的探讨来氟米特(LEF)对人肾间质成纤维细胞增殖和胶原合成的影响。方法在体外培养的人肾间质成纤维细胞中,加入不同浓度来氟米特活性代谢产物A771726和重组人结缔组织生长因子(rhCT-GF),MTT法测定两者单独及同时干预下细胞增殖情况;ELISA法测定细胞合成I、IV型胶原的含量。结果经不同浓度的rhCTGF刺激,成纤维细胞增殖和细胞合呈I型、IV型胶原均成剂量依赖性增加(P<0.01);而来氟米特作用细胞后,细胞增殖及胶原合成均呈剂量依赖性减少(P<0.01);在来氟米特与结缔组织生长因子(CTGF)共同作用下,细胞的增殖和胶原的合成较单用同剂量的CTGF时减少(P<0.05)。结论rhCTGF能够促进人肾间质成纤维细胞的增殖及I、IV型胶原合成;来氟米特则抑制细胞的增殖及细胞合成I、IV型胶原;来氟米特对rhCTGF诱导的胶原合成增加有一定的拮抗作用。

[Objective] To investigate the effect of connective tissue growth factor and leflunomide （LEF） on the proliferation of human renal interstitial fibroblasts （hRIFs） in vitro. [Methods] hRIFs were treated by different coneentrations of rhCTGF and A771726. eells proliferation were detected by MTT method. Type Ⅰ and type Ⅳ eollagen produeed by eells were determined by ELISA kits. [Results] In rhCTGF treated groups, the proliferation of hRIFs was inereased signifieandy （P 〈0.01）, while Type Ⅰ and type Ⅳ eollagen produeed by hRIFs was also inereased （P 〈 0.01）. In A771726 treated groups, the proliferation of the eells and Type Ⅰ and type Ⅳ eollagen produeed by hRIFs were decreased （P 〈0.01）. In rhCTGF＋A771726 treated groups, the proliferation of the eells and Type Ⅰ and type Ⅳ eollagen produeed by hRIFs were lower than the rhCTGF treated groups （P 〈0.05）. [Conclusion] CTGF inereasd the proliferation and the eollagen synthesis of hRIFs. LEF inhibited the proliferation and the eollagen synthesis of hRIFs direetly, moreover, it partly inhibited the the eollagen synthesis of hRIFs indueed by CTGF.