Mustoe T A, Landes A, Cromack D T, Mistry D, Griffin A, Deuel T F, Pierce G F
Department of Surgery, Washington University Medical Center, St. Louis, Mo.
Surgery. 1990 Aug;108(2):324-9; discussion 329-30.
Anastomotic dehiscence is a major cause of morbidity and mortality in gastrointestinal surgery. A unique model system of a gastric incision was developed to test the potential of polypeptide growth factors to enhance wound healing. Paired, deep partial-thickness incisions to but not including the gastric mucosa were made. A single topical application of transforming growth factor, type beta 1 (TGF-beta), platelet-derived growth factor, or control vehicle at the time of wounding was given. Wound breaking strength and detailed histologic analyses of wounds were evaluated as a function of time after wounding. TGF-beta (0.1 to 2.0 micrograms/wound) demonstrated a bimodal, dose-dependent acceleration of wound breaking strength 7 days after gastric wounding. An approximate 4-day acceleration of gastric wound breaking strength by TGF-beta (2 micrograms/wound) was seen at 7 and 11 days. Wounds treated with platelet-derived growth factor (10 micrograms/wound) displayed an increased cellular response but no enhancement of breaking strength at 7 and 11 days. These results demonstrate the ability of TGF-beta to accelerate gastrointestinal tissue repair by topical application and suggest significant potential for the use of growth factors in enhancing repair of surgical wounds of the gastrointestinal tract.
吻合口裂开是胃肠外科发病和死亡的主要原因。我们开发了一种独特的胃切口模型系统,以测试多肽生长因子促进伤口愈合的潜力。制作成对的、深达但不包括胃黏膜的部分厚度切口。在伤口形成时,局部单次应用转化生长因子β1(TGF-β)、血小板衍生生长因子或对照载体。伤口抗张强度和伤口的详细组织学分析作为伤口形成后时间的函数进行评估。TGF-β(0.1至2.0微克/伤口)在胃损伤7天后显示出双峰、剂量依赖性的伤口抗张强度加速。在第7天和第11天,TGF-β(2微克/伤口)使胃伤口抗张强度提前约4天增强。用血小板衍生生长因子(10微克/伤口)处理的伤口在第7天和第11天显示出细胞反应增加,但抗张强度没有增强。这些结果证明了通过局部应用TGF-β加速胃肠组织修复的能力,并表明生长因子在增强胃肠道手术伤口修复方面具有巨大潜力。