南方医科大学学报

南方医科大学学报 ›› 2006, Vol. 26 ›› Issue (10): 1383-1387.

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非诺贝特对TNF-α诱导的人脐静脉内皮细胞CD40表达和基质金属蛋白酶活性的抑制作用(英文)

林蓉； 刘俊田； 甘伟杰； 王维蓉； 韩纯洁； 刘瑜； 方志远；   

  1. 西安交通大学医学院药理学教研室； 西安交通大学医学院药理学教研室 西安交通大学环境与疾病相关基因教育部重点实验室； 陕西西安710061；
  • 出版日期:2006-10-20 发布日期:2006-10-20
  • 基金资助:
    Supported by National Natural Science Foundation of China (30371759),Key Science Research Project of Shaanxi Province (2005K10-G1) andNatural Science Foundation of Shaanxi Province (2005C250).

Fenofibrate inhibits tumor necrosis factor-α-induced expression of CD40 and matrix metalloproteinase in human vascular endothelial cells

LIN Rong1, 2, LIU Jun-tian1, GAN Wei-jie1, WANG Wei-rong1, HAN Chun-jie1, LIU Yu 1, FANG Zhi-yuan1 1Department of Pharmacology, 2Key Laboratories of Environment and Genes Related Diseases of Ministry of Education, Xi’an Jiaotong University, Xi’an 710061, China   

  1. 西安交通大学医学院药理学教研室； 西安交通大学医学院药理学教研室 西安交通大学环境与疾病相关基因教育部重点实验室； 陕西西安710061；
  • Online:2006-10-20 Published:2006-10-20

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摘要： 目的研究非诺贝特对肿瘤坏死因子-α(TNF-α)诱导的人脐静脉内皮细胞(HUVECs)CD40表达和基质金属蛋白酶(MMP)活性的作用。方法应用RT-PCR和流式细胞仪分别检测非诺贝特对TNF-α诱导的HUVECs的CD40mRNA和细胞表面CD40表达的影响;用明胶酶谱法测定TNF-α对HUVECs的MMP-2、MMP-9活性的影响以及非诺贝特对它们的作用。结果非诺贝特在5×10-5,1×10-4和2×10-4mol/L的浓度范围内能显著降低CD40mRNA和细胞表面CD40的表达(P<0.01),以1×10-4mol/L的非诺贝特的效果最为明显;浓度为2×10-4mol/L时,非诺贝特并没有进一步降低CD40mRNA和细胞表面CD40的表达。非诺贝特能抑制TNF-α诱导的HUVECs中MMP-2和MMP-9活性的增加。结论非诺贝特能降低TNF-α诱导的HUVECs的CD40表达,并且能抑制TNF-α诱导的HUVECs中MMP-2和MMP-9活性的增加。 

Abstract: Objective To investigate the regulatory effects of fenofibrate on TNF-α-induced CD40 expression and matrix metalloproteinase (MMP) activity in human vascular endothelial cells (HUVECs). Methods Quantitative RT-PCR and flow cytometry were employed to evaluate the effect of fenofibrate on TNF-α-induced CD40 mRNA and cell surface CD40 expression in HUVECs, and gelatin zymography was used to determine the effect of fenofibrate on the gelatinolytic activities of MMP-2 and MMP-9 in TNF-α-stimulated HUVECs. Results Fenofibrate at the concentrations of 5×10-5, 1×10-4 and 2×10-4 mol/L significantly reduced TNF-α-induced increment of CD40 mRNA and cell surface CD40 expressions (P<0.01), with the maximal inhibition achieved at the concentration of 1×10-4 mol/L. Fenofibrate at 2×10-4 mol/L did not further decrease CD40 expression induced by TNF-α. Fenofibrate significantly inhibited the stimulatory effect of TNF-α on MMP-2 and MMP-9 activities in HUVECs. Conclusion Fenofibrate reduces TNF-α-induced increment of CD40 expression and MMP-2 and MMP-9 activities in HUVECs. 

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