Egger B, Tolmos J, Procaccino F, Sarosi I, Friess H, Büchler M W, Stamos M, Eysselein V E
Division of Gastroenterology, Harbor-UCLA Medical Center, Torrance, California, USA.
Am J Surg. 1998 Jul;176(1):18-24. doi: 10.1016/s0002-9610(98)00104-4.
Inadequate healing and consequent leakage from bowel anastomoses are a significant cause of postoperative morbidity and mortality. Systemic application of keratinocyte growth factor (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 KGF administration on healing of colonic anastomoses in rats.
Rats underwent laparotomy, division of the left colon, and sigmoido-sigmoidostomy. KGF (5 mg/kg) or vehicle were administered intraperitoneally in two groups (n = 30 per group) 12 hours prior to surgery, and then once daily until sacrifice (6 animals per group; 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 days 2, 4, and 7 by 34%, 49%, and 19%, respectively. Histology, mucin staining, and measurements of the colonic crypt depth showed markedly less extended inflammation with an increased acidic mucin content and a significantly thickened mucosal layer in the KGF treated group when compared with vehicle-treated animals.
KGF promotes healing of colonic anastomoses in rats during a 1-week postoperative period following large bowel surgery. KGF may be acting to accelerate host reparative processes as well as to enhance protection of the anastomotic wound bed by increased colonic epithelium proliferation, increased mucus production, and reduction of the inflammatory activity at the anastomotic site.
肠道吻合口愈合不良及随之而来的渗漏是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KGF对大鼠结肠吻合口愈合的影响。
大鼠接受剖腹手术、左半结肠切断及乙状结肠-乙状结肠吻合术。两组（每组n = 30）在手术前12小时腹腔内给予KGF（5 mg/kg）或赋形剂，然后每天给药一次直至处死（每组6只动物；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34%、49%和19%。与赋形剂处理的动物相比，KGF处理组的组织学、黏蛋白染色和结肠隐窝深度测量显示炎症扩展明显减轻，酸性黏蛋白含量增加，黏膜层显著增厚。
KGF可促进大鼠大肠手术后1周内结肠吻合口的愈合。KGF可能通过增加结肠上皮细胞增殖、增加黏液分泌以及减少吻合部位的炎症活动，加速宿主修复过程并增强对吻合口创面的保护。
