羧胺三唑对TNF-α诱导的成纤维样滑膜细胞增殖及MMP-1、MMP-3表达的影响  

Effects of carboxyamidotriazole on the cell proliferation and the expressions of MMP-1 and MMP-3 in fibroblast-like synoviocytes stimulated by TNF-α

作　　者：朱蕾[1] 李娟[1] 武丹威[1] 罗丽丰 郭磊[1] 于晓丽[1] 叶菜英[1] 张德昌[1] 

机构地区：[1]中国医学科学院基础医学研究所北京协和医学院基础学院药理系,100005

出　　处：《中华临床医师杂志（电子版）》2013年第10期111-114,共4页Chinese Journal of Clinicians(Electronic Edition)

基　　金：国家自然科学基金(81102454);"重大新药创制"科技重大专项(2009ZX09102-049);中国医学科学院院所长基金(2010PY01;2010PY08)

摘　　要：目的研究羧胺三唑(CAI)对TNF-α诱导的佐剂性关节炎大鼠成纤维样滑膜细胞(FLS)增殖以及MMP-1、MMP-3表达的影响。方法用弗氏完全佐剂诱导大鼠佐剂性关节炎模型,并分离培养佐剂性关节炎大鼠的FLS。实验分为对照组,20 ng/ml TNF-α组,同时加入TNF-α和溶剂DMSO组,以及同时加入TNF-α和不同浓度CAI(10、20、40μmol/L)组。CCK-8法检测FLS的增殖反应,Western blot法检测MMP-1和MMP-3的蛋白表达。结果 20 ng/ml TNF-α能明显增加佐剂性关节炎大鼠FLS的增殖反应,增加MMP-1和MMP-3的蛋白表达(P<0.01)。CAI(20、40μmol/L)能够显著抑制TNF-α对佐剂性关节炎大鼠FLS的促增殖反应(P<0.01),抑制率分别为(31.13±7.07)%和(42.48±5.84)%,且CAI能够降低TNF-α诱导的MMP-1和MMP-3产生(P<0.01)。结论 CAI体外给药能够抑制TNF-α诱导的佐剂性关节炎大鼠FLS增殖以及产生MMP-1和MMP-3,这可能是其抗关节炎作用的机制之一。Objective To investigate the effects of carboxyamidotriazole（CAI） on the proliferation and the expressions of MMP-1 and MMP-3 in TNF-α-induced fibroblast-like synoviocytes（FLS） from adjuvant arthritis（AA） rats.Methods Freund＇s completed adjuvant was used to induce AA in rats,and FLS were separated and cultured from AA rats.AA FLS were stimulated by 20 ng/ml TNF-α with or without the vehicle DMSO or CAI （10,20,40 μmol/L）for 24 h,and the unstimulated group incubated only by the fresh medium was used as the control group.FLS proliferation was determined by CCK-8 method,and the protein expressions of MMP-1 and MMP-3 were measured by Western blot.Results The proliferation of FLS and the expressions of MMP-1 and MMP-3 were significantly increased under TNF-α stimulation（P 〈0.01）.CAI（20,40 μ mol/L）treatment suppressed the elevated proliferation of FLS stimulated by TNF-α （P 〈 0.01）,and the inhibition ratios were （31.13 ± 7.07） % and （42.48 ±5.84）%,respectively.In addition,CAI （20,40 μmol/L）inhibited MMP-1 and MMP-3 expressions in TNF-α-stimulated FLS（P〈0.01）.Conclusion CAI can inhibited TNF-α-induced proliferation and MMP-1 and MMP-3 productions in AA FLS which might be one of its anti-arthritic mechanisms.

关 键 词：肿瘤坏死因子α 细胞增殖 基质金属蛋白酶类 羧胺三唑 成纤维样滑膜细胞 

分 类 号：R965[医药卫生—药理学]