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应用血管内皮生长因子 (VEGF) ,对肢体缺血性疾病进行基因治疗的实验性研究 ,同时寻找适用于临床的、有效衡量肢体血液循环状况的检测指标。应用股动脉及其分支分离剔除术 ,造成新西兰兔下肢闭塞性血管病模型 ,术后立即于缺血骨骼肌部位多点注射 pcDNA3 .1 /VEGF16 5质粒 (n =1 2只 ) ,pcDNA3 .1空质粒 (n =8只 ) ,生理盐水(n =2 2只 )。选取不同时间点 ,行颈动脉插管造影 ,测量胫动脉压 ,检测双后肢膝关节的单位时间血流量、血流速度和红细胞浓度 ,检测肝肾功能 ,并进行病理取材 ,观察病理变化。结果显示 :术后对照组出现肢体缺血性坏死的动物数明显多于基因治疗组 ;血管造影显示 ,术后基因治疗组远端动脉充盈早于对照组 ,新生血管数目也明显多于同时期对照组 ;VEGF基因治疗组术后动脉血压的恢复也较对照组快。病理切片观察对照组骨骼肌出现萎缩坏死、间质纤维组织增生等缺血性病理改变的程度较基因治疗组重 ,质粒组新生血管明显多于对照组。结果提示 :利用肌肉细胞能够自主摄取裸DNA的特性 ,用重组VEGF质粒进行基因治疗 ,有效改善了缺血肢体的血液供应 ,并未出现严重不良反应
Application of vascular endothelial growth factor (VEGF), experimental study of gene therapy of limb ischemic disease, and find suitable for clinical, effective measurement of limb blood circulation detection indicators. The femoral artery and its branches were removed and excised, resulting in a model of occlusive vascular disease in New Zealand rabbits. Immediate injection of pcDNA3.1 / VEGF16 5 plasmid (n = 12) and pcDNA3.1 Empty plasmid (n = 8), saline (n = 2 2). At different time points, carotid artery catheterization angiography was performed to measure the tibia arterial pressure. The blood flow, blood flow velocity and erythrocyte concentration of the hind limbs of the hind limbs were measured. The liver and renal function were detected. Pathological changes were observed. The results showed that the number of animals with limb ischemic necrosis after operation in the control group was significantly more than that in the gene therapy group. Angiography showed that the distal arterial filling in the gene therapy group was earlier than that in the control group and the number of neovascularization was significantly more than that in the same period Control group; VEGF gene therapy group postoperative arterial blood pressure recovery is also faster than the control group. Pathological observation of skeletal muscle in the control group showed atrophy and necrosis, interstitial fibrosis and other ischemic pathological changes than the gene therapy group, the plasmid group of new blood vessels significantly more than the control group. The results suggest that the use of muscle cells can independently take the characteristics of naked DNA gene therapy with recombinant VEGF plasmid, effectively improve the blood supply of ischemic limbs, did not appear serious adverse reactions