血管损伤后TGF-β1/Smad信号通路在诱导BMSCs分化参与血管再狭窄的相关性研究  

Correlation study of TGF-1/Smad signaling pathway induced BMSCs differentiation and involvement in vascular restenosis after vascular injury

作　　者：郑仕杰 周敬群[1] 杨维华[1] 黄迪[1] 蔡金丹 戴秋婷 吕建峰 ZHENG Shijie;ZHOU Jingqun;YANG Weihua;HUANG Di;CAI Jindan;DAI Qiuting;LV Jianfeng(Department of Cardiovascular Medicine,Renhe Hospital Affiliated to Three Gorges University,Yichang 443000,China)

机构地区：[1]三峡大学附属仁和医院心血管内科

出　　处：《中国医药科学》2019年第17期50-54,共5页China Medicine And Pharmacy

基　　金：湖北省科技计划项目（2017CFC884）

摘　　要：目的观察转化生长因子-β1(TGF-β1)与骨髓间充质干细胞(BMSCs)在血管损伤后新生内膜中的表达,研究TGF-β1与BMSCs参与新生内膜修复的关系。方法选择右侧颈动脉内膜损伤的大鼠模型,实验分为6组,分别为对照组和实验组(实验组分5组:损伤0h、3d、7d、14d、21d组)。选取实验组各时间点的损伤血管组织,采用HE染色了解内膜增生导致损伤血管的狭窄水平,同时通过Westernblot法检测TGF-β1、p-Smad2/3、Smad2/3蛋白的表达、BMSCs标记物蛋白(Nestin)的表达,并检测与增殖标记物Ki-67的表达关系。结果(1)血管损伤后的不同时间点检测到新生内膜有不同程度的增生,以损伤组7d、14d、21d组新生内膜增生显著,与时间呈正相关,三组间比较差异有统计学意义(P<0.05);对照组与实验组(0h、3d组)未见新生内膜增生。(2)实验7d组的新生内膜中TGF-β1、p-Smad2/3、Smad2/3蛋白表达量开始升高,实验14d组达最高值,实验21d组表达量下降;且蛋白表达量与细胞增殖标记物Ki-67阳性指数呈正相关。(3)Western Blot法检测BMSCs标记物Nestin蛋白仅在7d、14d组中表达,并与TGF-β1的表达量正相关。结论(1)TGF-β1对血管损伤后内膜增生的促进作用可能通过Smad经典信号通路;(2)损伤血管的重建可能与TGF-β1的分泌招募BMSCs集聚损伤处有关,并诱导BMSCs向内膜细胞分化,最终共同参与新生内膜的形成。Objective To observe the protein expression of transforming growth factor-1(TGF-1)and bone mesenchymal stem cells(BMSCs)in the neointima after vascular injury,and to explore the relationship between the activation of TGF-1/Smad signal pathway and endometrial hyperplasia,as well as the relationship between TGF-1 and BMSCs recruitment.Methods The right common carotid artery injury model of rats by balloon catheterization was divided into the control group and the experimental group(five experimental groups:the injury groups at 0h,3d,7d,14d and 21d).The degree of vascular stenosis caused by intimal hyperplasia was observed by HE staining at different time points.The expression of TGF-1/Smad signaling pathway protein and BMSCs marker protein(Nestin)was detected by Westernblot,and the expression relationship with proliferation marker ki-67 was detected.Results(1)The degree of neointimal hyperplasia after vascular injury was detected at different time points.Significant neointimal hyperplasia was observed in the groups of 7d,14d and 21d after injury,and the difference between the three groups was statistically significant(P<0.05).No neointimal hyperplasia was observed in the control group and the experimental group(0h and 3d groups).(2)The protein expression levels of TGF-1,p-smad2/3 and smad2/3 in the neointima were detected by Westernblot.The results showed that the expression levels of TGF-1,p-smad2/3 and smad2/3 in the neointima were significantly increased on day 7,reaching the highest value on day 14,and decreased on day 21.The expression level was positively correlated with ki-67 positive index.(3)BMSCs marker Nestin protein was only expressed in groups of 7d and 14d by Westernblot,and was positively correlated with the expression level of TGF-1.Conclusion(1)The promotion effect of TGF-1 on intimal hyperplasia after vascular injury may be via the classical Smad signaling pathway.(2)The reconstruction of damaged blood vessels may be related to the secretion of TGF-1,recruitment of BMSCs to accumulate at the lesio

关 键 词：TGF-Β1/SMAD信号通路 骨髓间充质干细胞 血管损伤 

分 类 号：R654.3[医药卫生—外科学]