基础医学与临床 ›› 2007, Vol. 27 ›› Issue (2): 178-182.

• 研究论文 • 上一篇    下一篇

阿托伐他汀对oxLDL诱导的人单核-巨噬细胞MMP-9和组织因子的影响

童国新 王宁夫 陈鹏 张邢炜 徐坚 朱永良   

  1. 杭州市第一人民医院心内科 浙江大学医学院附属第二医院心内科 杭州市第一人民医院心内科 浙江大学医学院附属第二医院心内科
  • 收稿日期:2006-03-20 修回日期:2006-06-21 出版日期:2007-02-25 发布日期:2007-02-25
  • 通讯作者: 童国新

Effect of atorvastatin on MMP-9 and tissue factor induced by oxLDL in human monocytes-derived macrophages

  

  • Received:2006-03-20 Revised:2006-06-21 Online:2007-02-25 Published:2007-02-25

摘要: 目的 探讨他汀类降脂药潜在的降脂外机制。方法 人单核细胞来源的巨噬细胞与50mg/L的氧化低密度脂蛋白(oxLDL)共培养10d,加/不加入不同浓度的阿托伐他汀(0.01~0.5μmol/L);ELISA法测定基质金属蛋白酶-9(MMP-9)含量,酶谱学分析MMP-9活性;ELISA法测定组织因子(TF)表达,一期凝固法测定TF的促凝活性。结果 阿托伐他汀可剂量依赖性抑制单核-巨噬细胞的增殖,加入100μmol/L羟甲戊酸后这种抑制作用消失;0.1μmol/L和0.5μmol/L的阿托伐他汀可显著抑制单核-巨噬细胞MMP-9的表达和活性,以及抑制TF抗原的表达和促凝活性。结论 阿托伐他汀可抑制单核-巨噬细胞的增殖,亦可抑制单核-巨噬细胞引起的胶原降解活性和促凝活性。

Abstract: Objective To investigate the effect of atorvastatin-a HMG-CoA reductase inhibitor on the expression and activity of matrix metalloproteinase-9 (MMP-9) and tissue factor(TF) on human monocytes induced by Oxidized LDL (oxLDL).Methods Human monocytes-derived macrophages were incubated with oxLDL in presence or absence of different concentration atorvastatin.At the end of incubation,MMP-9 expression and its activity was assessed by ELISA and zymography analysis respectively,and TF expression and its procoagulant activity was assessed by ELISA and a one-stage clotting assay respectively. Results The results showed that atorvastatin inhibited human monocytes-derived macrophages proliferation in a methods of the concentration-dependment,which can be eliminated by adding 100μmol/L mevalonate. 0.1μmol/L and 0.5μmol/L atorvastatin can inhibit MMP-9 expression (1.32±0.06 VS 2.57±0.06μg/L,P<0.05;1.25±0.04 VS 2.57±0.06μg/L,P<0.05,respectively)and its activity of human monocytes-derived macrophages significantly,and inhibit TF expression(3.34±0.66 VS 5.78±0.86μg/L,P<0.05 ;2.20±0.60 VS 5.78±0.86μg/L,P<0.05,respectively) and its procoagulant activity in a methods of the concentration-dependment.Conclusion Atorvastatin inhibit the proliferation of human monocytes-derived macrophages,and also inhibit MMP-9 and TF expressions and their activities induced by oxLDL,which can lead to collagen degradation and blood clotting.