ENHANCED ANGIOGENESIS AND GROWTH OF COLLATERALS BY INVIVO ADMINISTRATION OF RECOMBINANT BASIC FIBROBLAST GROWTH-FACTOR IN A RABBIT MODEL OF ACUTE LOWER-LIMB ISCHEMIA - DOSE-RESPONSE EFFECT OF BASIC FIBROBLAST GROWTH-FACTOR
ENHANCED ANGIOGENESIS AND GROWTH OF COLLATERALS BY INVIVO ADMINISTRATION OF RECOMBINANT BASIC FIBROBLAST GROWTH-FACTOR IN A RABBIT MODEL OF ACUTE LOWER-LIMB ISCHEMIA - DOSE-RESPONSE EFFECT OF BASIC FIBROBLAST GROWTH-FACTOR
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DOI：
10.1016/0741-5214(92)90106-i
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发表时间：
1992-08-01
影响因子：
4.3
通讯作者：
FRIEDMANN, P
中科院分区：
文献类型：
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作者：
BAFFOUR, R;BERMAN, J;FRIEDMANN, P
本研究的目的是评价外源性重组碱性成纤维细胞生长因子（bFGF）对严重缺血组织床血管生成的影响。我们使用了两个阶段的程序，以产生严重缺血的后肢的34只新西兰兔。缺血侧后肢肌肉注射生理盐水（A组）、bFGF 1 μ g（B组）、bFGF 3 μ g（C组），每日1次，共2周。通过血管造影术、经皮血氧饱和度测定法（TcPO 2）、肌肉中氯化三苯基四氮唑还原的定量分光光度法、毛细血管密度（毛细血管/平方毫米）和毛细血管/肌纤维比评估组织灌注、骨骼肌梗死、血管生成和侧支生长。对于大腿和小腿测量，三组之间的基线TcPo 2无显著差异。血管造影显示，在所有评估的bFGF治疗动物的左后肢广泛灌注。在诱导缺血的14天内，所有组中大腿和小腿TcPo 2值均显示出显著增加（p < 0.0001），但两个治疗组表现出TcPo 2比对照组快得多的增加（p < 0.0001）。每平方毫米的毛细血管和毛细血管/肌纤维的比例显着增加，在所有的治疗后测量的所有动物接受bFGF。与基于氯化三苯基四唑还原的对照组相比，bFGF治疗组的大腿肌肉活力显著增加（p = 0.025）。A组和B组的两条大腿均存在肌肉梗死证据，而C组中无。在小腿水平，B组的肌肉活力有所改善，但A组和C组均观察到梗死（p = NS）。C组的结果表明，在大腿肌肉中高剂量的bFGF可能具有保护作用，但在缺血性更严重的小腿肌肉中可能导致梗死。一般而言，除小牛中氯化三苯基四唑盐减少外，所有给药后测量均存在剂量-反应效应趋势。我们的结论是，外源性碱性成纤维细胞生长因子可以促进严重缺血兔下肢血管新生和侧支循环的生长。
The purpose of this study was to evaluate the effects of exogenous recombinant basic fibroblast growth factor (bFGF) on angiogenesis in severely ischemic tissue beds. We used a two-stage procedure to produce severe ischemia of the hindlimb of 34 New Zealand rabbits. The ischemic hindlimb received intramuscular injection of saline (group A), 1-mu-g bFGF (group B), or 3-mu-g bFGF (group C), daily for 2 weeks. Tissue perfusion, skeletal muscle infarction, angiogenesis, and collateral growth were assessed by angiography, transcutaneous oximetry (TcPO2), quantitative spectrophotometric assay of triphenyltetrazolium chloride reduction in muscle, capillary density (capillaries per square millimeter), and capillary per muscle fiber ratio. There were no significant differences in baseline TcPo2 among the three groups for both thigh and calf measurements. Angiography revealed extensive perfusion of the left hindlimb in all the assessed bFGF treated animals. Both thigh and calf TcPo2 values showed a significant increase in all groups over the 14 days ischemia was induced (p < 0.0001), but the two treatment groups exhibited a much more rapid rise in TcPo2 than the control group (p < 0.0001). The capillaries per square millimeter and capillaries per muscle fiber ratios were significantly increased in all posttreatment measurements for all animals that received bFGF. The treatment groups with bFGF had a significant (p = 0.025) increase in thigh muscle viability compared with controls based on triphenyltetrazolium chloride reduction. Whereas there was evidence of muscle infarction in both the thighs of groups A and B, there was none in group C. At the level of the calf, there was improvement in muscle viability in group B, but infarction was seen in both groups A and C (p = NS). The results in group C suggest that a high dose of bFGF in the thigh muscle may be protective, but in the more ischemic calf muscle may cause infarction. Generally there was a trend toward a dose-response effect for all posttreatment measurements except triphenyltetrazolium chloride reduction in the calf. We conclude that exogenous bFGF can enhance angiogenesis and growth of collaterals in a severely ischemic rabbit lower limb.