Egger B, Tolmos J, Friess H, Sarosi I, Eysselein V E, Büchler M W
Klinik für Viszerale und Transplantationschirurgie, Universität Bern, Schweiz.
Langenbecks Arch Chir Suppl Kongressbd. 1998;115(Suppl I):95-9.
Inadequate healing and consequent leakage from large bowel anastomoses are a significant cause of morbidity and mortality following large bowel surgery. Systemic application of KGF has been shown to promote mucosal healing in models of colitis in rats and mice. The aim of the present study was to evaluate the effect of systemic Keratinocyte Growth Factor (KGF) administration on healing of colonic anastomoses in rats. Sprague-Dawley rats underwent laparotomy, division of the left colon and sigmoideo-sigmoideostomy. KGF (5 mg/kg) or its vehicle were administered intra-peritoneally 12 hours prior to surgery, and then once daily until sacrifice (2, 4, 7, 12 and 21 days after surgery). Bursting pressure measurements, histologic evaluation, morphometric analysis, mucin and collagen staining and hydroxyproline measurements of the anastomotic site were performed. Administration of KGF significantly increased anastomotic bursting pressure on postoperative day 2, 4 and 7 by +34%, +49% and +19%, respectively but not on day 12 and day 21. Histology, mucin staining and measurements of the colonic crypt depth showed markedly less extended inflammation, increased acidic mucin content and a significantly thickened mucosal layer in the KGF treated group when compared to vehicle treated animals. Hydroxyproline content and collagen staining were not different between KGF and vehicle treated animals. We conclude that KGF promotes healing of colonic anastomoses in rats during a one week postoperative period. KGF may be acting to accelerate host reparative processes as well as to enhance protection of the anastomotic wound bed by increased epithelium proliferation, increased mucus production and reduction of the inflammatory activity at the anastomotic site.
大肠吻合口愈合不良及随之而来的渗漏是大肠手术后发病和死亡的重要原因。在大鼠和小鼠结肠炎模型中，已证明全身应用角质形成细胞生长因子（KGF）可促进黏膜愈合。本研究的目的是评估全身给予角质形成细胞生长因子（KGF）对大鼠结肠吻合口愈合的影响。将Sprague-Dawley大鼠进行剖腹手术，分离左结肠并进行乙状结肠-乙状结肠吻合术。在手术前12小时腹腔内注射KGF（5mg/kg）或其溶媒，然后每天注射一次直至处死（术后2、4、7、12和21天）。对吻合部位进行爆破压力测量、组织学评估、形态计量分析、黏蛋白和胶原蛋白染色以及羟脯氨酸测量。给予KGF后，术后第2、4和7天的吻合口爆破压力分别显著增加了34%、49%和19%，但在第12天和第21天没有增加。与溶媒处理的动物相比，组织学、黏蛋白染色和结肠隐窝深度测量显示，KGF处理组的炎症扩展明显减少、酸性黏蛋白含量增加且黏膜层显著增厚。KGF处理组和溶媒处理组动物的羟脯氨酸含量和胶原蛋白染色没有差异。我们得出结论，KGF在术后一周内可促进大鼠结肠吻合口的愈合。KGF可能通过加速宿主修复过程以及通过增加上皮细胞增殖、增加黏液分泌和减少吻合部位的炎症活动来增强对吻合口创面床的保护。
