Ibukiyama C
Second Department of Internal Medicine, Tokyo Medical College, Japan.
Jpn Heart J. 1996 May;37(3):285-300. doi: 10.1536/ihj.37.285.
Angiogenic therapy using fibroblast growth factor (FGF) and vascular endothelial growth factor (VEGF) is being developed as a novel therapeutic strategy to obtain restoration of blood flow around the ischemia in cases of ischemic cardiovascular disease. In addition, arterial gene therapy through gene transfer by VEGF genes has now reached the stage of clinical application. Through in vivo animal experiments to determine the angiogenic effects of FGF and VEGF, we hope to obtain clues concerning the clinical applications of these methods. Methods-1: Twenty-three adult dogs were divided into 3 groups as follows: Group A-1: 20 micrograms of bFGF was administered intravenously simultaneously with heparin three times per week in 4 dogs. Group A-2: 20 micrograms of bFGF was administered intravenously three times a week without heparin in 4 dogs. Group B: 20 micrograms of bFGF was administered intramuscularly three times per week in 5 dogs. Group C: Sham operation control group consisting of 10 dogs. Local ischemia was created in the hind limbs of animals in groups A-1, A-2 and B through ligation of the femoral artery. Selective femoral arteriography was performed immediately after ligation at 1 week and 2 weeks postoperatively. Biopsy was also performed either at 1 week or 2 weeks after ligation. Results-1: (1) The percent increase in number of collateral vessels of the ischemic zone, as recognized on arteriography, was greater in the bFGF groups compared to group C. (2) The increase in collateral vessels peaked at 1 week. (3) No difference in angiogenic effect was observed in relation to the method of administration. (4) The combined administration of heparin had no angiogenic effect. (5) The hemoglobin content of the biopsy specimens was significantly greater in the 3 groups receiving bFGF compared to group C. Methods-2: The same study was performed using VEGF as detailed in Method-1. Results-2: As in the first experiment, a significant increase in collateral vessels was seen in the VEGF group compared to the control group. Both exogenous bFGF and VEGF significantly promote collateral vessel development and appear to be effective novel therapeutic agents for the treatment of ischemic disease.
使用成纤维细胞生长因子（FGF）和血管内皮生长因子（VEGF）的血管生成疗法正在作为一种新的治疗策略进行开发，以在缺血性心血管疾病病例中实现缺血周围血流的恢复。此外，通过VEGF基因进行基因转移的动脉基因疗法现已进入临床应用阶段。通过体内动物实验来确定FGF和VEGF的血管生成作用，我们希望获得有关这些方法临床应用的线索。方法-1：将23只成年犬分为3组如下：A-1组：4只犬，每周静脉注射20微克碱性成纤维细胞生长因子（bFGF），同时每周三次注射肝素。A-2组：4只犬，每周静脉注射20微克bFGF三次，不注射肝素。B组：5只犬，每周肌肉注射20微克bFGF三次。C组：假手术对照组，由10只犬组成。通过结扎股动脉在A-1组、A-2组和B组动物的后肢造成局部缺血。在结扎后1周和2周立即进行选择性股动脉造影。在结扎后1周或2周也进行活检。结果-1：（1）在动脉造影中，与C组相比，bFGF组缺血区侧支血管数量的增加百分比更大。（2）侧支血管的增加在1周时达到峰值。（3）在给药方法方面未观察到血管生成作用的差异。（4）肝素联合给药无血管生成作用。（5）与C组相比，接受bFGF的3组活检标本的血红蛋白含量显著更高。方法-2：使用VEGF按照方法-1中详述的进行相同的研究。结果-2：与第一个实验一样，与对照组相比，VEGF组侧支血管有显著增加。外源性bFGF和VEGF均显著促进侧支血管发育，似乎是治疗缺血性疾病的有效的新型治疗药物。
