川芎嗪对颈动脉球囊损伤后基质金属蛋白酶组织抑制物-1基因表达的影响

Effect of ligustrazine on intimal proliferation and expression of tissue inhibitor of matrix metalloproteinase-1 in balloon-injured rabbit carotid artery

目的观察川芎嗪对兔颈动脉球囊损伤后新生内膜增生、管腔狭窄度和管壁基质金属蛋白酶组织抑制物-1(TIMP-1)表达的影响,探讨其预防再狭窄的可能机制和作用。方法应用直径为3 mm的球囊导管制作家兔左颈动脉去内皮损伤模型,术后14 d测量对照组和川芎嗪治疗组动物新生内膜及中膜厚度、新生内膜面积和管腔狭窄度,并应用Brdu和α-actin免疫组化方法观察新生内膜细胞的增殖指数,同时应用半定量逆转录聚合酶链式反应(RT-PCR)方法比较对照组和治疗组间管壁TIMP-1的基因表达。结果治疗组新生内膜及中膜厚度、新生内膜面积、管腔狭窄度和细胞增殖指数均低于对照组,而川芎嗪治疗组动脉壁TIMP-1mRNA的表达明显高于对照组。结论川芎嗪具有明显增加动脉损伤后管壁TIMP-1mRNA形成的作用,从而抑制新生内膜的形成和降低管腔狭窄度。

Objective To study the influence of ligustrazine on neointima, stenotic rate of arterial lumen and expression of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) of arterial wall in rabbit carotid artery after balloon injury for evaluating the possibility of the mechanism and function of ligustrazine on the prevention of restenosis. Methods Artery injury models in deendothelialization of the left carotid artery of rabbits were completed by using balloons catheter 3mm in diameter. Neointimal thickness, medial thickness, neointimal area and stenotic ratio of arterial lumen were measured, proliferation index of neointimal cells were observed by the method of Brdu and α-actin immunohistochemistry and contents of tissue inhibitor of matrix metalloproteinase-1 (TIMP-1) mRNA of arterial walls were measured by RT-PCR between drug groups and control groups at 14 days after balloon injury. Results Treatment regimen produced significant reductions in neointimal thickness, medial thickness, neointimal area, stenotic rate of arterial lumen and proliferation index of cells in neointima, but the content of TIMP-1 mRNA of arterial walls in therapy group was significantly higher than control group. Conclusion Ligustrazine has a significant role of inhibiting neointimal formation and reducing stenotic ratio of arterial lumen after balloon injury through elevating the content of TIMP-1 mRNA of injured artery walls.