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

Objective-To evaluate the effects of keratinocyte growth factor (KGF) on in testinal adaptation after resection of 85% of the small intestine and consi der 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% re section of the small intestine, while the other two groups were sham-operat ed, undergoing transection and reanastomosis. Resected and sham-operated gr oups 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 thi s growth in the resected animals. Mucosal wet weight of the small intestine increased with resection and was further increased (by 20% or more) with K GF administration. Mucosal thickness, villus length, and crypt depth exhibi ted similar patterns of response. The KGF-induced increase in mucosal morph ology was accompanied by increased mucosal DNA and protein content, followe d by a trend toward increased mucosal enzyme activity. Histology demonstrat ed an increase in goblet cells in KGF-treated animals. In situ hybridizatio n analysis demonstrated that KGF markedly increased mucosal expression of i ntestinal trefoil protein (ITF) mRNA. Conclusions-KGF enhances gut growth, differentiation, and gene regulation d uring adaptation in rat small intestine after massive resection. Clinical Relevance-KGF may be beneficial in the management of veterinary an d human patients undergoing massive intestinal resection. (C)Copyright 2000 by The American College of Veterinary Surgeons.