血管内皮生长因子和转化生长因子β_1在兔动脉损伤后内膜中表达及意义

Expressions of vascular endothelial growth factor and transforming growth factor-beta1 by the intima of balloon-injured rabbit carotid arteries

目的观察血管内皮生长因子基因(VEGFmRNA)和转化生长因子β1基因(TGF-β1mRNA)在兔颈动脉球囊损伤后内膜增生过程中的动态表达,探讨VEGF和TGF-β1与兔颈动脉球囊损伤后再狭窄的关系。方法健康雄性家兔40只,随机分为正常对照组(10只),实验I、II、III组(每组各10只),实验组行右颈总动脉血管成形术,并分别于术后第1、2和4周各处死实验I、II、III组,第4周同时处死对照组兔。用光镜观察内膜损伤后形态学变化,用原位杂交技术动态观察血管壁VEGFmRNA和TGF-β1mRNA的表达情况,并进行图像分析。结果与对照组比,实验组内膜面积呈持续性显著增加(P<0.05),管腔面积从第2周开始呈持续性显著减少(P<0.01)。对照组VEGFmRNA呈弱阳性表达,TGF-β1mRNA无表达。实验组VEGFmRNA呈弱阳性表达,与对照组比差异无统计学意义(P>0.05),但TGF-β1mRNA呈持续高表达(P<0.01)。结论TGF-β1参与促进兔颈动脉球囊损伤后内膜增生和管腔狭窄,VEGF不参与兔颈动脉球囊损伤后内膜增生和管腔狭窄。

Objective To establish a rabbit model of restenosis and analyze the expressions of VEGFmRNA and TGF-β1mRNA during the intimal proliferation. We also explored the relationship between VEGFmRNA, TGF-β1mRNA and restenosis. Methods 40 healthy male New Zealand white rabbits were evenly divided into three injury groups and one control group. Right carotid arteries were injured with PCI balloon in the injury groups. 10 rabbits of each injury group were sacrificed on weeks 1, 2 and 4 after the injury, VEGFmRNA and TGF- β1mRNA were examined by in situ hybridization, All the samples were analyzed using a computerized imaging analysis system. Results In the injury groups, neointimal areas were significantly larger than those in control group（ P 〈 0. 05 or P 〈 0. 01 ） , and luminal areas were smaller than those in control group from the 2nd week（ P 〈 0. 01 ）. Expressions of TGF-β1 mRNA in injury groups were obviously upregulated and significantly higher than those in control groups（ P 〈0. 01 ）. The expressions of VEGFmRNA were not different between the injury groups and the control group. Conclusions After rabbit carotid artery balloon injury, TGF-β1 played an important role in the induction of intimal proliferation and restenosis while VEGF was not involved.