目的: 冠状动脉旁路移植术( Coronary artery bypass grafting，CABG) 后静脉桥再狭窄发生率高，组织
蛋白酶S( Cathepsin S，CatS) 在血管再狭窄中起着重要作用，本研究即验证CatS 基因敲除后对静脉桥再狭窄有抑
制作用。方法: 选取CatS 基因敲除后的小鼠作为实验组( 36 只) ，以C57BL/6 小鼠为对照组( 36 只) 。利用Cuff
套管技术建立小鼠下腔静脉－颈动脉移植模型，显微镜观察血管内膜增生来证实CatS 基因敲除后对静脉桥的再
狭窄有抑制作用，通过酶联免疫吸附法( enzyme－linked immuno sorbent assay，ELISA) 测定MMP－9 酶的含量，进
一步探讨CatS 基因敲除后抑制CABG 静脉桥再狭窄的作用机制。结果: 在静脉移植术后早期两组内膜增生无
显著差别，随着术后时间的推移，对照组小鼠内膜程度较实验组变化较为明显，且CatS( － /－) 组MMP－9 含量表
达较C57BL/6 组明显减少，尤其是在术后2wk，实验组( CatS( － /－) 组) 和对照组( C57 BL/6 组) MMP－9 含量表
达分别为6．12±0．11ng /mL 和9．23±0．12ng /mL，两组比较P＜0．05，差异有统计学意义。结论: CatS 基因敲除后在
一定程度上能对静脉桥再狭窄有抑制作用，并且通过巨噬细胞MMP－9 含量减少作用的途径，证实其可以抑制
内皮细胞及血管平滑肌细胞增殖反应，细胞外基质沉积，减轻静脉桥血管的再狭窄。

Objective: Coronary artery bypass grafting( CABG) is an effective method for treatment
of coronary heart disease，but the high incidence of venous bridge restenosis after CABG．One study
found that cathepsin S( CathepsinS，CatS) play an important role in the vascular restenosis．The purpose
of this study is confirm the inhibitory effect after Cathepsin S knockout to the venous bridge restenosis．
Methods: The experimental group as the mice of after Cathepsin S gene knockout as the research object
( 36) ， the C57 BL /6 mice，as control group( 36) ．Using the Cuff casing technology establish inferior vena
cava－carotid artery transplantation model in mice．By identifying gene knockout，a microscope neointimal
hyperplasia to confirm the inhibitory effect to the venous bridge restenosis after Cathepsin S
knockout．At the same time by the enzyme－linked immunosorbent method( enzyme－linked immunosorbent
assay，ELISA) to determine the content of MMP－9 enzymes to explore the mechanism of restenosis
inhibition of CABG after Cathepsin S knockout．Ｒesults: At the different time points after venous transplantation(
8h，1 d，3 d，7 d and 14 d and 28 d) ， in early postoperative，endometrial hyperplasia showed
no statistically significant difference between the two groups．With the extension of time after venous
transplantation， the CatS( － / －) contents of MMP－9 express decreased significantly with the C57 BL /6
group contrast．Especially in 2 weeks postoperatively， the experimental group( CatS( － / －) group) and
control group( group C57 BL /6) expression of MMP－9 content respectively 6．12±0．11ng /mL and 9．23
± 0．12 ng /mL，comparing the two groups P ＜ 0．05，the difference was statistically significant．
Conclusion: Through microscope observe the neointimal hyperplasia confirmed the inhibitory effect of
venous bridge restenosis after CatS gene knockout．By means of macrophages MMP－9 content reducing
effect，confirmed that it can inhibit the endothelial cells and vascular smooth muscle cell proliferation，
extracellular matrix deposition， relieve venous bridge vascular restenosis．

Ｒ6

 收稿日期: 2017－10－23; 修回日期: 2017－12－24
基金项目: 内蒙古自治区自然科学基金( 2016MS6830)
作者简介: 张华锋( 1988－) ，男，山东省鱼台县人民医院胸外科住院医师。
通讯作者: 高荣，硕士研究生导师，主任医师，E－mail: Gaorong1002@ sina．com 内蒙古医科大学附属医院， 010050