上海交通大学学报（医学版）

›› 2010, Vol. 30 ›› Issue (5): 522-.

• 论著（基础研究） • 上一篇    下一篇

反义Smad3转染阻断TGF-β1信号转导对球囊损伤后大鼠血管内膜增生的影响

王嵩浩, 盛 净, 蔡文玮, 陆 平, 陈 谊, 马绍骏   

  1. 上海交通大学 医学院第九人民医院老年病科, 上海 200011
  • 出版日期:2010-05-25 发布日期:2010-05-28
  • 通讯作者: 盛 净, 电子信箱: shengjing60@163.com。
  • 作者简介:王嵩浩（1984—）, 男, 硕士生；电子信箱: wangsonghao8276953@163.com。
  • 基金资助:

    上海市教委基金（06BZ016）

Effects of TGF-β1 signal transduction inhibition by antisense-Smad3 adenovirus vector transfection on intimal hyperplasia after balloon injury in rats

WANG Song-hao, SHENG Jing, CAI Wen-wei, LU Ping, CHEN Yi, MA Shao-jun   

  1. Department of Geriatrics, The Ninth People's Hospital, School of Medicine, Shanghai Jiaotong University, Shanghai 200011, China
  • Online:2010-05-25 Published:2010-05-28
  • Supported by:

    Shanghai Education Committee Foundation, 06BZ016

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摘要：

目的 通过建立大鼠颈动脉球囊损伤模型并体内转染反义Smad3腺病毒载体，研究阻断TGF-β1/Smad3信号途径对损伤后大鼠颈动脉内膜增生的影响。方法 90只SD大鼠随机分为单纯损伤组（单纯球囊损伤大鼠颈动脉内膜）、干预组（损伤后局部保留灌注反义Smad3腺病毒液）、空白对照组（损伤后局部灌注空载腺病毒液）；另取6只同周龄大鼠作为正常对照组（不进行任何处理）。各组分别在损伤后第1天、3天、1周、2周、1月、3月时处死大鼠并取材。ELISA法检测单纯损伤组和正常对照组不同时间点血清中TGF-β1的质量浓度；Real-time PCR和HE染色法分别检测三个损伤组在不同时间点Smad3 mRNA表达和血管壁内膜、中膜厚度。结果 单纯损伤组各时间点TGF-β1的质量浓度较正常对照组显著升高（P<0.05）。干预组第1天、3天、1周、2周、1月时的Smad3 mRNA表达和第1天、2周、3月时的内膜/中膜比值均较单纯损伤组明显下降（P<0.05）；单纯损伤组与空白对照组各指标比较差异均无统计学意义（P>0.05）。结论 体内转染反义Smad3可以阻断TGF-β1/Smad3信号转导，从而抑制内膜增生。

关键词: 球囊损伤, 内膜增生, TGF-β1/Smad3信号通路, 反义Smad3, 腺病毒

Abstract:

Objective To investigate the effects of antisense-Smad3 adenovirus vector transfection on carotid intimal hyperplasia after balloon injury in rats. Methods Ninety SD rats were randomly divided into injury group (balloon injury on carotid intima), intervention group (antisense Smad3 adenovirus vector transfection after balloon injury) and blank control group (blank adenovirus vector transfection after balloon injury). Another six age-matched rats were served as control groups (without any treatment). Rats in each group were sacrificed 1 d, 3 d, 1 week, 2 weeks, 1 month and 3 months after injury, and samples were harvested. The serum concentrations of TGF-β1 in injury group and normal control group of different time points were determined by ELISA. The expression of Smad3 mRNA of carotid artery in injury group, intervention group and blank control group was detected by Real-time PCR, and the carotid intima and media thickness was measured by HE staining. Results The serum concentrations of TGF-β1 of each time point in injury group were significantly higher than those of normal control group (P<0.05). The expression of Smad3 mRNA 1 d, 3 d, 1 week, 2 weeks and 1 month after injury and intima/media thickness ratios 1 d, 2 weeks and 3 months after injury in intervention group were significantly lower than those in injury group (P<0.05), while there was no significant difference in the expression of Smad3 mRNA and intima/media thickness ratios between injury group and blank control group (P>0.05). Conclusion Antisense-Smad3 adenovirus vector transfection can block TGF-β1/Smad3 signal transduction, and inhibit intimal hyperplasia.

Key words: balloon injury, intimal hyperplasia, TGF-β1/Smad3 signaling pathway, antisense Smad3, adenovirus