前纤维蛋白1在糖基化终末产物介导内皮损伤中的作用
DOI:
作者:
作者单位:

作者简介:

通讯作者:

基金项目:

国家自然科学青年基金资助项目(81000140)


The Role of Profilin-1 in Endothelial Injury Mediated by Advanced Glycation End Products
Author:
Affiliation:

Fund Project:

  • 摘要
  • |
  • 图/表
  • |
  • 访问统计
  • |
  • 参考文献
  • |
  • 相似文献
  • |
  • 引证文献
  • |
  • 资源附件
    摘要:

    目的 通过体外培养的人脐静脉内皮细胞,探讨糖基化终末产物对内皮细胞的损伤及与前纤维蛋白1的关系。方法 在体外培养的内皮细胞,分别用不同浓度(100、200、400 mg/L)糖基化终末产物孵育不同时间(6、12、24、48 h),采用Western blot检测细胞前纤维蛋白1的表达,免疫荧光染色检测前纤维蛋白1的表达和F肌动蛋白形态及分布,同时检测细胞上清液非对称性二甲基精氨酸、一氧化氮、细胞间黏附分子水平和细胞内活性氧的水平。结果 糖基化终末产物呈时间依赖性上调内皮细胞前纤维蛋白1的表达,以200 mg/L糖基化终末产物作用最为明显;对照组F肌动蛋白分布在细胞周边,分布均匀,细胞间连接紧密;200 mg/L糖基化终末产物处理24 h后,细胞内F肌动蛋白形态和分布发生明显改变,同时伴有胞浆中前纤维蛋白1的表达增高;200 mg/L糖基化终末产物孵育内皮细胞24 h可显著降低一氧化氮水平,升高非对称性二甲基精氨酸、细胞间黏附分子、活性氧水平,诱导内皮细胞损伤;用siRNA干扰前纤维蛋白1表达可显著抑制糖基化终末产物诱导的内皮损伤,表现为降低细胞前纤维蛋白1的表达,明显改善F肌动蛋白的结构和分布,增加一氧化氮的生成,降低非对称性二甲基精氨酸和细胞间黏附分子的水平。结论 糖基化终末产物通过上调前纤维蛋白1的表达诱导血管内皮细胞损伤。

    Abstract:

    Aim To investigate the effect of profilin-1 on the process of endothelial cell damage mediated by advanced glycation end product(AGE)in cultured human umbilical vein endothelial cell(HUVEC). Methods The endothelial cells were incubated by AGE with different concentrations(100, 200, 400 mg/L)and times(6, 12, 24, 48 h). The protein expression of profilin-1 were determined by Western blot. The morphology and distribution of F-actin was detected by immunofluorescent staining. The levels of asymmetric dimethylargnine(ADMA), intercellular adhesion molecule-1(ICAM-1), nitric oxide(NO)in cultured condition and reactive oxygen species(ROS)were detected by related kits. Results Compared with control, profilin-1 protein expression was significantly up-regulated after treatment with 200 mg/L AGE for 24 h, concomitantly with the markedly increased levels of ICAM-1, ADMA and ROS and the significantly decreased levels of NO. Compared with control, the morphology and distribution of F-actin was significantly altered by AGE. Interfering with the profilin-1 gene expression can protect the extent of cell damage induced by AGE by down-regulating the protein expression of profilin-1, improving the distribution of F-actin, decreasing the levels of ICAM-1 and ADMA and increasing the levels of NO. Conclusion AGE induced endothelial cell damage by upregulating the expression of profilin-1

    参考文献
    相似文献
    引证文献
引用本文

李振宇,谢秀梅,杨天伦,陈美芳.前纤维蛋白1在糖基化终末产物介导内皮损伤中的作用[J].中国动脉硬化杂志,2015,23(01):11~16.

复制
分享
文章指标
  • 点击次数:
  • 下载次数:
历史
  • 收稿日期:2014-06-09
  • 最后修改日期:
  • 录用日期:
  • 在线发布日期: