摘要
目的研究超声造影剂SonoVue携带血管内皮生长因子(VEGF)基因靶向转染兔损伤动脉后血管内皮功能的恢复及程度。方法构建真核表达质粒pCDNA3.1(-)/hVEGF165。建立兔髂外动脉的球囊损伤模型,并随机分为两组:损伤后血管腔内注射携带VEGF基因质粒的造影剂并接受超声辐照的为实验组,损伤后无任何干预为对照组。2周后超声检测髂外动脉内皮依赖性舒张功能,完成后将兔处死取损伤处血管,HE染色计算血管内膜与中膜面积比值,免疫组化了解血管壁平滑肌细胞的增殖和VEGF的表达情况。结果实验组髂外动脉血管内皮依赖性舒张功能较对照组改善(P<0.05),但实验组的血管内膜面积与中膜面积比值与对照组比较,差异无统计学意义(P>0.05)。免疫组化显示实验组血管壁平滑肌细胞增殖核抗原表达明显减低,且见大量VEGF阳性反应的棕褐色颗粒。结论靶向超声介导VEGF基因转染损伤的动脉管壁2周即可有效改善局部血管的内皮功能,有效增强VEGF的表达,并且抑制平滑肌细胞增殖,提示携基因靶向超声可以为早期改善介入治疗后血管内皮功能并由此防治再狭窄提供新途径。
Objective To investigate the recovery of vascular endothelial function （VEF） after vascular endothelial growth factor（VEGF） gene transfeetion with ultrasound contrast agent SonoVue in injured arteries of rabbits. Methods The plasmid pCDNA3.1 （ - ）/hVEGF165 was constructed. The rabbits with injured iliac artery were randomly divided into two groups： VEGF plasmid - loaded microbubbles were injected into the injured arteries with ultrasound irradiation in experiment group, while the control group was treated without any intervention. After two weeks, the endothelial independent dilation （EDD） of the iliac artery was measured by ultrasonography. After the rabbits were sacrificed, the injured arteries were collected for pathology examination. The intimaL/media area ratio was calculated by HE stain, the expression level of VEGF and the proliferation of vascular smooth muscle cells（VSMCs） was performed by immunohistochemistry. Results Compared with control group, EDD was significantly increased in experiment group （ P 〈 0.05 ） , while there was no significant difference in intimal/ media area ratio between two groups （ P 〉 0.05 ）. Immunohistochemistry showed proliferating cell nuclear antigen （ PCNA ） activity was obviously decreased in experiment group, and many VEGF positive cells could be detected. Conclusion Targeted ultrasound - mediated VEGF gene transfection can improve VEF, enhance expression of VEGF and inhibit the proliferation of VSMCs. This might provide a novel promising approach for improving the vascular endothelial function after interventional treatment and preventing vascular restenosis.
出处
《临床超声医学杂志》
2011年第9期577-580,共4页
Journal of Clinical Ultrasound in Medicine
基金
南京市科技发展计划项目(200504021)
南京市医学科技发展项目(ZKX07003)
关键词
靶向超声
VEGF基因
血管内皮功能
兔
Targeted ultrasound
VEGF gene
Vascular endothelial function
Rabbits
