Keratinocyte growth factor enhances early gut adaptation in a rat model of short bowel syndrome

Objective-To evaluate the effects of keratinocyte growth factor (KGF) on intestinal adaptation after resection of 85% of the small intestine and consider its potential application in short bowel syndrome (SBS). Study Design-Experimental study using a known model of SBS. Animal Population-Thirty male Sprague Dawley rats. Methods-Four groups of animals were designated. Two groups underwent 85% resection of the small intestine, while the other two groups were sham-operated, undergoing transection and reanastomosis. Resected and sham-operated groups then received either 3 mg/kg KGF or vehicle subcutaneously daily for 3 days. Gut adaptation was evaluated by measurements of mucosal cellularity and biochemical activity in duodenal, jejunal, and ileal segments. Results-Significant small intestinal growth after bowel resection alone was confirmed in resected versus sham-operated rats. KGF further augmented this growth in the resected animals. Mucosal wet weight of the small intestine increased with resection and was further increased (by 20% or more) with KGF administration. Mucosal thickness, villus length, and crypt depth exhibited similar patterns of response. The KGF-induced increase in mucosal morphology was accompanied by increased mucosal DNA and protein content, followed by a trend toward increased mucosal enzyme activity. Histology demonstrated an increase in goblet cells in KGF-treated animals. In situ hybridization analysis demonstrated that KGF markedly increased mucosal expression of intestinal trefoil protein (ITF) mRNA. Conclusions-KGF enhances gut growth, differentiation, and gene regulation during adaptation in rat small intestine after massive resection. Clinical Relevance-KGF may be beneficial in the management of veterinary and human patients undergoing massive intestinal resection. (C)Copyright 2000 by The American College of Veterinary Surgeons.