Wang Xiao Tian, Liu Paul Y, Tang Jin Bo
Department of Surgery, Roger Williams Medical Center, Providence, RI 02908, USA.
Plast Reconstr Surg. 2006 Jan;117(1):129-37; discussion 138-9. doi: 10.1097/01.prs.0000185609.07293.3e.
Gene therapy is a novel approach for enhancing the viability of ischemic flaps. Expression of growth factor genes pertinent to angiogenesis and activation of genes of relevant signal pathways are imperative for improving flap viability. The authors investigated the gene expression profiles of growth factors and signal transduction pathways in ischemic flaps after PDGF gene therapy.
Twenty Sprague-Dawley rats were divided into two groups. The experimental group (n = 10) received the plasmid vector containing the PDGF cDNA injected into the dermis of the flap area, whereas the control group (n = 10) received the physiologic saline. Seven days later, a dorsal random flap was raised. Seven days after surgery, flap viability was assessed, and expression of VEGF, bFGF, TGF-beta1, NF-kappaB, Erk2, Stat1, and Smad2 genes of the NF-kappaB, MAPK, JAK-STAT, and Smad pathways was assessed by quantitative analysis of the products of reverse-transcriptase polymerase chain reaction.
Transfer of exogenous PDGF gene significantly improved flap viability (p = 0.011). Levels of expression of VEGF and bFGF genes in the flap were significantly elevated after PDGF gene transfer (p = 0.0001 and p = 0.001, respectively). Expression of the NF-kappaB gene was significantly elevated (p = 0.041). In contrast, expression of TGF-beta1, and Erk2, Stat1, and Smad2 genes was not changed.
Transfer of exogenous PDGF gene to ischemic flaps promotes expression of VEGF and bFGF genes and activation of NF-kappaB gene in addition to its effects on the PDGF gene. The finding implies that transfer of the gene of one growth factor ultimately improves the expression of the genes of multiple growth factors. Activation of the NF-kappaB gene suggests that the NF-kappaB pathway may be important in enhancement of flap viability and will likely be a target of future efforts of regulation of signaling process in treatment of ischemic flaps.
基因治疗是提高缺血皮瓣存活率的一种新方法。与血管生成相关的生长因子基因的表达以及相关信号通路基因的激活对于提高皮瓣存活率至关重要。作者研究了血小板衍生生长因子（PDGF）基因治疗后缺血皮瓣中生长因子和信号转导通路的基因表达谱。
将20只Sprague-Dawley大鼠分为两组。实验组（n = 10）将含有PDGF cDNA的质粒载体注射到皮瓣区域的真皮中，而对照组（n = 10）注射生理盐水。7天后，掀起背部随意皮瓣。术后7天，评估皮瓣存活率，并通过逆转录聚合酶链反应产物的定量分析评估NF-κB、丝裂原活化蛋白激酶（MAPK）、Janus激酶-信号转导子和转录激活子（JAK-STAT）以及Smad信号通路中血管内皮生长因子（VEGF）、碱性成纤维细胞生长因子（bFGF）、转化生长因子-β1（TGF-β1）、NF-κB、细胞外信号调节激酶2（Erk2）、信号转导子和转录激活子1（Stat1）以及Smad2基因的表达。
外源性PDGF基因的转染显著提高了皮瓣存活率（p = 0.011）。PDGF基因转染后皮瓣中VEGF和bFGF基因的表达水平显著升高（分别为p = 0.0001和p = 0.001）。NF-κB基因的表达显著升高（p = 0.041）。相比之下，TGF-β1、Erk2、Stat1和Smad2基因的表达没有变化。
将外源性PDGF基因转染至缺血皮瓣除了对PDGF基因产生影响外，还能促进VEGF和bFGF基因的表达以及NF-κB基因的激活。这一发现表明，一种生长因子基因的转染最终可改善多种生长因子基因的表达。NF-κB基因的激活表明，NF-κB信号通路可能在提高皮瓣存活率中起重要作用，并且很可能成为未来调控缺血皮瓣信号转导过程治疗研究的靶点。
