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山东大学学报(医学版) ›› 2011, Vol. 49 ›› Issue (4): 13-16.

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雌激素受体对血管平滑肌细胞早衰的影响

李群锋   

  1. 衢州职业技术学院医学院形态教研室, 浙江 衢州 324000
  • 收稿日期:2010-09-20 出版日期:2011-04-10 发布日期:2011-04-10
  • 作者简介:李群锋(1982- ),男,硕士研究生,主要从事心血管病方面的研究。 E-mail:liqunfenglenny@sina.com

Effects of the estrogen receptor on stress-induced premature senescence of  vascular smooth muscle cells in vitro

LI Qun-feng   

  1. Department of Morphology, Medical School of Quzhou College of Technology, Quzhou 324000, Zhejiang, China
  • Received:2010-09-20 Online:2011-04-10 Published:2011-04-10

摘要:

目的      探讨雌激素受体对血管平滑肌细胞(VSMCS)早衰的影响及其机制。方法     体外培养的第2~3代雌性SD大鼠VSMCS分为实验组和对照组,在有或无不同浓度(10-10mol/L~10-8mol/L)雌激素受体激动剂(PPT/DPN)存在时,用150μmol/L H2O2诱导早衰。采用流式细胞术检测衰老相关标志物(DcR2)、Pull down assay,Western blotting等方法检测原癌基因Ras的表达或活性。结果     流式细胞术检测显示,H2O2组血管平滑肌细胞DcR2表达率显著增高(P﹤0.05)。H2O2+PPT及H2O2+DPN各浓度组血管平滑肌细胞DcR2表达率均低于H2O2组,且随激动剂浓度增高而降低,但不同激动剂之间无显著差别(P﹥0.05)。H2O2组细胞内GTPRas/Total Ras比值显著高于对照组(P﹤0.05),在有10-8mol/L PPT或DPN存在时,细胞内的GTP-Ras/Total Ras比值明显降低,但仍高于对照组。H2O2+PPT组和H2O2+DPN组之间差异无统计学意义(P﹥0.05)。结论     在介导雌激素的抗早衰效应上,雌激素受体a(ERa)和雌激素受体b(ERb)可能具有同等效应;雌激素抗早衰效应机制之一可能是抑制原癌基因Ras的激活。

关键词: 雌激素受体;血管平滑肌细胞;早衰

Abstract:

Objective    To explore the effects and mechanism of the estrogen receptor on stressinduced premature senescence of vascular smooth muscle cells (VSMCS). Methods     The VSMCS, cultured from female SD rats and followed by 23 vitro passages , were induced into senescence by exposure to 150μmol/L H2O2 in the presence or absence of different concentrations (10-10mol/L-10-8mol/L) of PPT/DPN. Expressions of senescence associated marker (DcR2) were detected by flow cytometry. Expressions or activities of the protooncogene Ras were detected by pull-down assay and Western blotting analysis.   Results     Flow cytometry analysis showed that in physiological concentrations, the estrogen receptor agonist significantly inhibited H2O2promoted highlevel expression of DcR2 of VSMCS in a dosedependent manner(P﹤0.05). Pulldown assay and Western blotting analysis revealed that administration of (10-10mol/L-10-8mol/L) of PPT/DPN obviously reduced the H2O2-induced activity of Ras(P﹤0.05).  Conclusion     The estrogen receptor exerts inhibitive effect on stress-induced senescence of VSMCS by suppressing activity of Ras. ERa and ERb may have the same effects on stress-induced premature senescence of vascular smooth muscle cells in vitro.

Key words: Estrogen receptor; Vascular smooth muscle cells; Stress inducedsenescence

中图分类号: 

  • R772
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