Department of Plastic Surgery, Rhode Island Hospital, Brown University School of Medicine, Providence, USA.
Wound Repair Regen. 2011 Jul-Aug;19(4):498-504. doi: 10.1111/j.1524-475X.2011.00705.x. Epub 2011 Jun 7.
Necrosis of surgically transferred flaps due to ischemia is a serious wound problem. We evaluated the improvement of flap survival and changes in angiogenic gene expression profiles after transfer of the VEGF gene by means of adeno-associated virus type 2 (AAV2) vector to rat ischemic flaps. Thirty rats were divided into one experimental group, one AAV2-GFP group, and one saline group. AAV2-VEGF or AAV2-GFP were injected intradermally into the rat dorsum in the AAV2-VEGF or AAV2-GFP group. The saline group received saline injection. A 3 × 10 cm flap was raised in each rat two weeks post-injection. One week after surgery, flap viability was evaluated. Angiogenesis real-time PCR array was performed to analyze the expression of angiogenesis-associated genes. The AAV2-VEGF treatment significantly improved flap survival (p<0.05). Immunohistochemical staining showed increased VEGF expression in AAV2-VEGF treated flaps. The PCR array identified remarkable changes in 6 out of the 84 angiogenesis-associated genes in AAV2-VEGF treated flaps. Particularly, EGF, PDGF-A and VEGF-B genes were up-regulated in these flaps. In contrast, FGF2 gene expression was down-regulated. In conclusion, AAV2-VEGF improves flap survival and affects the expression of a series of endogenous growth factor genes, which likely play critical roles in the enhancement of ischemic flap survival.
由于缺血导致的外科移植皮瓣坏死是一个严重的伤口问题。我们通过腺相关病毒 2 型（AAV2）载体将 VEGF 基因转染至大鼠缺血皮瓣，评估了皮瓣存活率的提高和血管生成基因表达谱的变化。30 只大鼠分为实验组、AAV2-GFP 组和盐水组。在 AAV2-VEGF 或 AAV2-GFP 组中，将 AAV2-VEGF 或 AAV2-GFP 皮内注射至大鼠背部。盐水组接受盐水注射。在注射后两周，每只大鼠都掀起了一个 3×10cm 的皮瓣。术后一周，评估皮瓣的存活情况。进行血管生成实时 PCR 阵列分析以分析与血管生成相关的基因表达。AAV2-VEGF 治疗显著提高了皮瓣的存活率（p<0.05）。免疫组织化学染色显示 AAV2-VEGF 处理的皮瓣中 VEGF 表达增加。PCR 阵列鉴定出 AAV2-VEGF 处理的皮瓣中有 6 个（84 个）与血管生成相关的基因发生了显著变化。特别是，EGF、PDGF-A 和 VEGF-B 基因在这些皮瓣中上调。相反，FGF2 基因表达下调。总之，AAV2-VEGF 可提高皮瓣存活率，并影响一系列内源性生长因子基因的表达，这可能在增强缺血皮瓣存活率方面发挥关键作用。
