吉林大学学报(医学版)

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辛伐他汀对血管内皮祖细胞复制性衰老的抑制作用及其机制

杜岗1，周丽1，常青2，李自成1   

  1. 1.暨南大学附属第一医院心内科，广东 广州510630;2.暨南大学医学院组织学与胚胎学系，广东 广州510632）〖JP〗
  • 收稿日期:2013-04-16 出版日期:2013-09-28 发布日期:2013-09-28
  • 通讯作者: 李自成 E-mail:（Tel：020-38688620，E-mail：zichengli@163.net）
  • 作者简介:杜 岗（1978-），男，山西省长治市人，主治医师，在读医学博士，主要从事心血管疾病的基础与临床研究。
  • 基金资助:

    广东省科技厅科技计划项目资助课题(2010-1096-136)；广东省广州市科技计划项目资
    助课题(2010Y1-C941)；暨南大学第一临床医学院重点学科基金资助课题 (2010-4)

Inhibitory effect of simvastatin on replicative senescence of endothelial progenitor cells and its mechanism

DU Gang1,ZHOU Li1,CHANG Qing2,LI Zi-cheng1   

  1. (1.Department of Cardiology,First Affiliated Hospital,Jinan University,Guangzhou 510630， China；2.Department of Histology and Embryology,College of Medical Sciences,Jinan University,Guangzhou 510632，China)
  • Received:2013-04-16 Online:2013-09-28 Published:2013-09-28

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摘要：

目的：探讨辛伐他汀对血管内皮祖细胞(EPCs)复制性衰老的影响，阐明辛伐他汀抗衰老的作用机制。方法：取第2代EPCs作为正常对照组，取第8代细胞作为实验组，分为高剂量辛伐他汀组（培养基中的辛伐他汀浓度为1×10－7 mol?L-1）、低剂量辛伐他汀组(培养基中的辛伐他汀浓度为1×10－8 mol?L-1)和复制性衰老细胞组。继续培养7 d，流式细胞术检测各组细胞凋亡率、细胞周期以及Bcl-2蛋白的表达水平。结果：正常对照组细胞的早期凋亡率和晚期凋亡率低于其他3组 (P<0.05或P<0.01)；高剂量辛伐他汀组、低剂量辛伐他汀组和复制性衰老细胞组3组间早期凋亡率比较差异无统计学意义(P>0.05)；与复制性衰老细胞组比较，高剂量辛伐他汀组和低剂量辛伐他汀组细胞的晚期凋亡率降低(P<0.01或P<0.05)，高剂量辛伐他汀组与低剂量辛伐他汀组之间的细胞晚期凋亡率比较差异无统计学意义(P>0.05)。与正常对照组比较，高剂量辛伐他汀组、低剂量辛伐他汀组和复制性衰老细胞组细胞大部分停滞于G0/G1期，S期及G2/M期减少(P<0.01)；实验组3组之间各细胞周期细胞比例比较差异无统计学意义(P>0.05)。正常对照组细胞Bcl-2蛋白表达的荧光强度和阳性表达率均明显高于其他3组(P<0.01）；高剂量辛伐他汀组的荧光强度和阳性表达率高于复制性衰老
组(P<0.05或P<0.01），低剂量辛伐他汀组的阳性表达率高于复制性衰老组(P<0.01），但荧光强度与复制性衰老组比较差异无统计学意义（P>0.05)。结论：辛伐他汀可能通过降低Bcl-2蛋白的表达来延缓EPCs的复制性衰老。

关键词: 内皮祖细胞, 辛伐他汀, 复制性衰老, 细胞凋亡, Bcl-2

Abstract:

Abstract:Objective
To investigate the effect of simvastatin on replicative senescence of endothelial progenitor cells (EPCs) and to clarify the anti-senescence mechanism of simvastatin.Methods The second generation of EPCs were used as normal control group,and the eighth generation cells were divided into high dose simvastatin group,low dose simvastatin group,and replicative senescence group.The cell cycle and apoptosis,the expression of Bcl-2 protein were detected by flow  cytometry  after the next 7 d culturing.Results The early  and late apoptotic rates of the EPCs in normal control group were lower than those in the other three groups (P<0.05 or P<0.01);there was no statistical difference in the early apoptotic rates between high dose simvastatin group,low dose simvastatin group and replicative senescence(P>0.05).The differences of late apoptotic rate between replicative senescence group,high dose simvastatin group and low dose simvastatin group were statistically significant (P<0.05 or P<0.01).The percentages of EPCs in high dose simvastatin group,low dose simvastatin group and replicative senescence group were increased in the G0/G1 phase,but were  decreased in the phases of S and G2/M compared with  normal control group (P<0.01),but there was no difference between simvastatin groups and replicative senescence group(P>0.05).Compared with normal control group,the mean fluorescence intensities and the positive expression rates of Bcl-2 protein in high dose simvastatin group,low dose simvastatin group and replicative senescence group were significantly decreased(P<0.01);and the differences between high dose simvastatin group and replicative senescence group were also statistically significant(P<0.05 or P<0.01);the positive expression rate of Bcl-2 protein in low dose simvastatin group was higher than that in replicative senescence group (P<0. 01),but the difference of the mean fluorescence intensity between two groups had no statistical significance（P>0.05).Conclusion Simvastatin can reduce the replicative senescence of EPCs,and the mechanism may be related to decreasing the expression of Bcl-2 protein.

Key words: endothelial progenitor cells, simvastatin, replicative senescence, apoptosis, Bcl-2

中图分类号: 

  • R96
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