Insulin-like growth factor I and truncated keratinocyte growth factor accelerate healing of left-sided colonic anastomoses.

Abstract

Human full-length keratinocyte growth factor (KGF) promotes healing of colon anastomoses in rats through mechanisms other than enhancement of collagen synthesis. Since insulin-like growth factor (IGF) I increases matrix synthesis, the aim of this study was to evaluate the effect of systemic truncated KGF (tKGF), IGF-I and combined tKGF-IGF-I administration on the healing of colonic anastomoses in rats. Rats underwent laparotomy, division of the left colon, and sigmoidosigmoidostomy. tKGF (1 mg/kg), IGF-I (1 mg/kg), tKGF-IGF-I (both 1 mg/kg) or vehicle was administered intraperitoneally in four groups (n = 18 per group) 12 h before surgical intervention, and then once daily until killing (six animals per group; 2, 4 and 6 days after surgery). Bursting pressure measurements, histological evaluation, morphometric analysis, mucin and collagen staining, and 5-bromo-2'-deoxyuridine (BrdU) immunohistochemistry of the anastomotic site were undertaken. Administration of tKGF, IGF-I and the combination of both growth factors significantly increased anastomotic bursting pressure at postoperative day 2 (63, 71 and 113 per cent respectively), day 4 (68, 83 and 80 per cent) and day 6 (48, 43 and 43 per cent) compared with the control group. No intergroup differences were found. Histological examination, mucin and BrdU staining, and measurement of colonic crypt depth indicated less inflammation, increased acidic mucin content, a higher crypt cell proliferation rate and thickened mucosal layer in the growth factor-treated animals than in controls. Enhanced collagen staining was observed only in IGF-treated animals. tKGF and IGF-I markedly accelerate the healing of colonic anastomoses in rats. However, combined administration of the two growth factors does not show additional benefit. Both growth factors may be acting to accelerate host reparative processes as well as to enhance protection of the anastomotic wound bed.