Department of Surgery, Oregon Health & Science University, Portland, Oregon, USA.
Dis Esophagus. 2012 Jul;25(5):456-64. doi: 10.1111/j.1442-2050.2011.01247.x. Epub 2011 Sep 7.
Proper anastomotic healing is dependent upon many factors including adequate blood flow to healing tissue. The aim of this study was to investigate the impact of vascular endothelial growth factor (VEGF(165)) transfection on anastomotic healing in an ischemic gastrointestinal anastomosis model. Utilizing an established opossum model of esophagogastrectomy followed by esophageal-gastric anastomosis, the gastric fundus was transfected with recombinant human vascular endothelial growth factor via direct injection of a plasmid-based nonviral delivery system. Twenty-nine animals were divided into three groups: two concentrations of VEGF and a control group. Outcomes included VEGF mRNA transcript levels, neovascularization, tissue blood flow, and anastomotic bursting pressure. To determine whether local injection resulted in a systemic effect, distant tissues were evaluated for VEGF transcript levels. Successful gene transfection was demonstrated by quantitative polymerase chain reaction analysis of anastomotic tissue, with significantly higher VEGF mRNA expression in treated animals compared to controls. At the gastric side of the anastomosis, there was significantly increased neovascularization, blood flow, and bursting pressure in experimental animals compared to controls. There were no differences in outcome measures between low- and high-dose VEGF groups; however, the high-dose group demonstrated increased VEGF mRNA expression across the anastomosis. VEGF production was not increased at distant sites in treated animals. In this animal model, VEGF gene therapy increased VEGF transcription at a healing gastrointestinal anastomosis without systemic VEGF upregulation. This treatment led to improved healing and strength of the acutely ischemic anastomosis. These findings suggest that VEGF gene therapy has the potential to reduce anastomotic morbidity and improve surgical outcomes in a wide array of patients.
吻合口的正常愈合取决于多种因素，包括愈合组织的足够血流。本研究旨在探讨血管内皮生长因子（VEGF(165)）转染对缺血性胃肠道吻合口愈合的影响。利用已建立的袋狸食管胃切除术和食管胃吻合术模型，通过质粒非病毒传递系统直接注射重组人血管内皮生长因子，对胃底进行转染。29 只动物分为三组：两种浓度的 VEGF 和对照组。结果包括 VEGF mRNA 转录水平、新生血管形成、组织血流和吻合口爆裂压。为了确定局部注射是否会产生全身效应，评估了远处组织的 VEGF 转录水平。通过定量聚合酶链反应分析吻合组织，成功地进行了基因转染，与对照组相比，治疗组的 VEGF mRNA 表达明显升高。在吻合口的胃侧，与对照组相比，实验组的新生血管形成、血流和爆裂压显著增加。低剂量和高剂量 VEGF 组之间的结果测量没有差异；然而，高剂量组在整个吻合口处显示出更高的 VEGF mRNA 表达。治疗动物的远处部位没有增加 VEGF 产生。在这种动物模型中，VEGF 基因治疗在愈合的胃肠道吻合口增加了 VEGF 转录，而没有全身 VEGF 上调。这种治疗方法导致急性缺血吻合口的愈合和强度得到改善。这些发现表明，VEGF 基因治疗有可能减少吻合口发病率，并改善广泛患者的手术结果。
