睾酮通过芳香化酶途径抑制人血管内皮细胞单核细胞趋化蛋白1的基因表达
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Testosterone Reduces Mrna Level of Chemoattractant Protein of Human Umbilical Vein Endothelial Cell by Aminoglutethimide
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    摘要:

    目的探讨睾酮对脐静脉内皮细胞生成单核细胞趋化蛋白1的影响与机制,分析睾酮与内皮细胞功能及动脉粥样硬化的关系。方法脂多糖刺激体外培养的脐静脉内皮细胞,培养液中分别加入不同浓度睾酮(3×10-10、3×10-9、3×10-8、3×10-6mol/L和3×10-5mol/L),ELISA实验方法检测细胞上清液单核细胞趋化蛋白1蛋白含量,RT-PCR方法检测单核细胞趋化蛋白1 mRNA相对水平。培养液中加入雄激素受体拮抗剂或芳香化酶抑制剂,重复上述实验。结果与空白对照组(374.16±10.2)比较,3×10-10mol/L睾酮组上清液单核细胞趋化蛋白1蛋白含量明显增加(424.50±11.3,p<0.05),随着睾酮浓度增加,单核细胞趋化蛋白1逐渐减少,3×10-5mol/L组差异具有统计学意义(292.29±12.6,p<0.01)。与对照组比较,3×10-9,3×10-6,3×10-5mol/L组单核细胞趋化蛋白1mRNA水平明显降低。雄激素受体拮抗剂可逆转3×10-10mol/L睾酮对单核细胞趋化蛋白1对蛋白生成的影响,芳香化酶抑制剂可削弱睾酮对内皮细胞单核细胞趋化蛋白1基因表达与蛋白合成的抑制作用。结论睾酮浓度降低,可促进血管内皮细胞发生炎症反应;睾酮达到生理浓度抑制内皮细胞发生炎症反应,这种作用是睾酮通过细胞内芳香化酶转化为雌激素实现的。

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    Aim To investigate the effects of different level testosterone on production of monocyte chemoattractant protein-1(MCP-1) in HUVEC and possible mechanism,so as to study the relationship between atherosclerosis and testosterone. Method After foreclosed HUVEC with LPS and different testosterone(control,3×10-10 mol/L,physiological concentration 3×10-9 and 3×10 -8 mol/L,3×10-6,3×10-5 mol/L),protein production of MCP-1 was examined by ELISA and mRNA level by RT-PCR.To study the mechanism,we added Fluramide or Aminoglutethimide beforehand in the medium for 5 hours and reduplicated above experimental processes. Results In contrast to control,protein production of lower testosterone was significantly increased and this effect was contracted by fluramide;while protein production were significantly decreased by 3×10-5 mol/L testosterone and mRNA level decreased by 3×10-9,3×10-6,3×10-5 mol/L testosterone,those effects were weakened by aminoglutethimide.Conclusion Lower testosterone may stimulate inflammation of HUVEC;testosterone of physiological level or above could suppress HUVEC from inflammation and dysfunction by converting to estradiol.

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黄明学,富路,李丽敏,高倩萍,周立君,陈彦东.睾酮通过芳香化酶途径抑制人血管内皮细胞单核细胞趋化蛋白1的基因表达[J].中国动脉硬化杂志,2007,15(12):899~902.

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  • 收稿日期:2007-05-24
  • 最后修改日期:2007-12-14
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