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目的 通过转染人血管内皮细胞生长因子 (phVEGF)基因促使血管内支架处内皮细胞生长以预防支架内再狭窄的发生。方法 将 phVEGF基因局部涂布于由多聚赖氨酸包被的血管内支架上 ,采用介入方法经颈静脉插管至 6只狗的右肝静脉 ,同时以置入裸支架为对照组。结果 支架置入后第 1周 ,在转染 phVEGF基因组局部血管组织内 ,RT PCR法检测到 phVEGF的表达 ;荧光显微镜下观察到部分血管内皮细胞发出黄绿色荧光 ;扫描电镜显示支架腔内皮分化程度较对照组高。置入后第 8周 ,转染 phVEGF基因组 (n =6 )血管造影显示支架通畅 ,而对照组 (n =5 )则均发生再狭窄 ;支架端肝静脉血管平均新生内膜厚度 ,平均新生内膜面积 ,百分狭窄面积均明显小于对照组 [(0 .16 7± 0 .10 3)mm比 (1.96 5± 0 .72 5 )mm ,(2 .5 6 8± 1.5 2 6 )mm2 比 (17.5 96± 7.939)mm2 ,(11.46 2± 5 .42 3) %比 (6 8.5 0 5± 2 4.0 0 3) %,P <0 .0 5 ];免疫组化显示平滑肌细胞增殖程度 (PLI)也显著高于对照组 [(0 .0 30± 0 .0 0 2 )比 (0 .0 42± 0 .0 0 3) ,P <0 .0 5 ) ]。结论 phVEGF基因涂布支架可加速支架内皮化的形成 ,进而抑制血管内支架置入术后血栓形成和内膜增殖引起的再狭窄发生。
Objective To promote the growth of endothelial cells in vascular stents by transfection of human vascular endothelial cell growth factor (phVEGF) gene to prevent in-stent restenosis. Methods The phVEGF gene was locally coated on the endovascular stent coated with poly-L-lysine. The right hepatic vein was cannulated via the jugular vein with 6 stents through the jugular vein. At the same time, the bare scaffold was used as the control group. Results In the first week after stent implantation, phVEGF expression was detected by RT PCR in phVEGF-transfected local vascular tissues. Some endothelial cells fluoresced yellow-green fluorescence under fluorescence microscope. Endothelial cell differentiation was observed by scanning electron microscopy Higher than the control group. At 8 weeks post-implantation, angiography of the phVEGF-transfected group (n = 6) showed that the stent was unobstructed, while the control group (n = 5) had restenosis; mean neointimal thickness The area of membrane and percentage of stenosis were significantly lower than that of the control group [(0.167 ± 0.103) mm (1.96 5 ± 0.72 5) mm, (2.56 ± 1.52 6) mm2 (17.5 96 ± 7.939) mm2, (11.46 ± 5.42 3)% (6 8.5 05 ± 2 4.0 0 3)%, P 0.05]. Immunohistochemistry showed that the proliferation of smooth muscle cells (PLI ) Was significantly higher than that in the control group [(0.30 ± 0.002) vs (0.042 ± 0.303, P <0.05)]. Conclusion phVEGF gene coated scaffold can accelerate the formation of scaffold endothelialization, and then inhibit the restenosis caused by thrombosis and intimal hyperplasia after endovascular stent implantation.