Zheng Zhen-hua, Xu Liang, Fan Xi-hong
Department of General Surgery, General Hospital of Jinan Military Region, Jinan, Shandong, P. R. China 250031.
Zhongguo Xiu Fu Chong Jian Wai Ke Za Zhi. 2004 Mar;18(2):142-5.
To investigate the feasibility of intramuscular gene therapy for acute arterial ischemic diseases by use of plasmid pcDNA3-VEGF121 and to evaluate therapeutic efficiency of vascular endothelial growth factor (VEGF) by different routes of administration.
Fifty New Zealand White rabbits were randomly assigned to either gelation sponge carrying-pcDNA3-VEGF121 (n = 18), intramuscular injection-pcDNA3-VEGF121 (n = 18), or pcDNA3 (as control group, n = 14). After ligation of the external iliac artery and complete excision of the femoral artery, 500 micrograms of the plasmid pcDNA3-VEGF121 were transfected into the muscles of the ischemic limb by gelation sponge carrying or direct intramuscular-injection. Immediately after gene transfection, blood flow of the internal iliac artery were measured. VEGF121 gene expression was detected by RT-PCR after 2 days, 1 week, 2 weeks, 3 weeks and 4 weeks of transfection. After 30 days, blood flow of the internal iliac artery, angiographic score and histological vessels of ischemic hindlimbs were measured respectively.
In the two VEGF-treated groups, VEGF121 mRNA expressed in the transfected ischemic muscles after 2 days and lasted 2 weeks. Immediately after gene transfection, blood flow of the internal iliac artery had no significant difference between three groups. After 30 days, blood flow of the internal iliac artery, angiographic score and capillary density were significantly greater in both VEGF-treated groups than in control group. Complexity of vascular branching and vessel density of gelation sponge-VEGF treated limbs were significantly greater when compared with the intramuscular-injection limbs.
These findings suggest the feasibility of employing gene therapy of pcDNA3-VEGF121 could augment collateral development and tissue perfusion in an animal model of hindlimb ischemia, and gelation sponge carrying VEGF gene may respect a potential therapy methods.
探讨应用质粒pcDNA3-VEGF121进行急性动脉缺血性疾病肌肉内基因治疗的可行性，并评估血管内皮生长因子（VEGF）不同给药途径的治疗效果。
将50只新西兰白兔随机分为明胶海绵携带pcDNA3-VEGF121组（n = 18）、肌肉注射pcDNA3-VEGF121组（n = 18）或pcDNA3组（作为对照组，n = 14）。在结扎髂外动脉并完全切除股动脉后，通过明胶海绵携带或直接肌肉注射将500微克质粒pcDNA3-VEGF121转染至缺血肢体的肌肉中。基因转染后立即测量髂内动脉的血流量。转染后2天、1周、2周、3周和4周通过RT-PCR检测VEGF121基因表达。30天后，分别测量髂内动脉的血流量、血管造影评分和缺血后肢的组织学血管情况。
在两个VEGF治疗组中，转染后2天缺血肌肉中表达VEGF121 mRNA，并持续2周。基因转染后立即，三组间髂内动脉血流量无显著差异。30天后，两个VEGF治疗组的髂内动脉血流量、血管造影评分和毛细血管密度均显著高于对照组。与肌肉注射组相比，明胶海绵-VEGF治疗组肢体的血管分支复杂性和血管密度显著更高。
这些发现表明，采用pcDNA3-VEGF121基因治疗可增加后肢缺血动物模型中的侧支循环发育和组织灌注，携带VEGF基因的明胶海绵可能是一种潜在的治疗方法。
