Holzbach T, Taskov C, Neshkova I, Holm P S, Konerding M A, Schams D, Gänsbacher B, Biemer E, Giunta R E
Abteilung für Plastische und Wiederherstellungschirurgie, Klinikum rechts der Isar, Technische Universität München.
Handchir Mikrochir Plast Chir. 2005 Dec;37(6):365-74. doi: 10.1055/s-2005-872992.
A regular tissue functioning requires the adequate supply of oxygen and nutrient via blood vessels. The sequences of formation and maturation of vessels are initiated and maintained by different growth factors. The VEGF growth factor plays an exceptional role in these mechanisms. The creation of sublethal ischemia as an angiogenic stimulus known as "Delay" is a well established procedure in plastic surgery, although the underlying molecular biological mechanisms still remain unknown. The important role of VEGF and its regulation depending on oxygen pressure suggest a strong connection between this growth factor and the delay phenomenon. The VEGF concentration in skin and underlying muscle was measured in overdimensioned random pattern flaps on 32 male Sprague-Dawley rats after either VEGF gene therapy or circumcision without elevation of the flap and compared to controls. Additional random pattern flaps were raised seven days post gene therapy or delay. The effect on the flap perfusion was measured postoperatively using Indocyanine green Laser Fluoroscopy and the size of the surviving and necrotic areas of the flaps were analysed. The skin of the random pattern flaps showed both in the Delay group and in the VEGF gene therapy group a significantly elevated VEGF concentration compared to the controls. The underlying rectus abdominis muscle showed no significant differences in VEGF concentration between the groups. The flap perfusion postoperatively was significantly increased solely in the VEGF gene therapy group. The analysis of the surviving area of the flaps showed a significant increase over the controls in the gene therapy group. The Delay procedure results in a significantly and locally raised concentration of the VEGF growth factor. The gene therapeutical use of this growth factor allows us to raise flap perfusion and to reduce necrosis. Both VEGF gene therapy and Delay seem to promote similar mechanisms whereas the gene therapy produced superior results in this setting.
正常组织的功能需要通过血管充分供应氧气和营养物质。血管形成和成熟的过程由不同的生长因子启动和维持。血管内皮生长因子（VEGF）在这些机制中发挥着特殊作用。在整形外科中，制造亚致死性缺血作为一种称为“延迟”的血管生成刺激是一种成熟的手术方法，但其潜在的分子生物学机制仍然未知。VEGF的重要作用及其对氧分压的依赖性调节表明该生长因子与延迟现象之间存在密切联系。在32只雄性Sprague-Dawley大鼠身上，对超尺寸随机型皮瓣在进行VEGF基因治疗或环切术后（不掀起皮瓣）的皮肤及皮下肌肉中的VEGF浓度进行了测量，并与对照组进行比较。在基因治疗或延迟7天后掀起额外的随机型皮瓣。术后使用吲哚菁绿激光荧光透视法测量皮瓣灌注情况，并分析皮瓣存活和坏死区域的大小。随机型皮瓣的皮肤在延迟组和VEGF基因治疗组中均显示VEGF浓度比对照组显著升高。皮下腹直肌在各组之间的VEGF浓度无显著差异。术后仅在VEGF基因治疗组皮瓣灌注显著增加。皮瓣存活面积分析显示基因治疗组比对照组有显著增加。延迟手术导致VEGF生长因子浓度显著且局部升高。该生长因子的基因治疗应用使我们能够提高皮瓣灌注并减少坏死。VEGF基因治疗和延迟似乎都促进了相似的机制，而在这种情况下基因治疗产生了更好的结果。
