A COMPARISON OF THE EFFECT OF GROWTH-FACTORS ON INTESTINAL FUNCTION AND STRUCTURE IN SHORT-BOWEL SYNDROME

Background/Purpose: Epidermal growth factor (EGF) and Insulin like gro wth factor-1 (IGF-1) increase substrate absorption beyond the normal a daptive response after massive small bowel resection in the rat.(1) Ho wever, the mechanism for this response is unknown. This study was desi gned to evaluate the ultrastructural features of the rat small intesti ne epithelium after exposure to EGF and IGF-I and correlate any change s with a possible hypothesis regarding the mechanism for the increased absorption. Methods: Male Sprague-Dawley rats underwent an 80% small bowel resection and jejunostomy tube placement. Seven days later an os motic pump placed subcutaneously and containing the test substance was connected to the jejunostomy tube. The rats were assigned to one of t hree groups: group 1 received normal saline (control, n = 5); group 2 received EGF at 150 mu g/kg/d (n = 5); and group 3 received IGF-1 at 2 0 mg/kg/d (n = 5). After a 14-day infusion, a portion of mid-small bow el was resected for light and electron microscopic evaluation from eac h of the animals, The following features were compared between the gro ups: villous length, crypt length, villous-crypt ratio, villi per mill imeter mucosa, goblet cell distribution, eosinophilic infiltrates, num ber and distribution of organelles, length of microvilli, and complete ness of microvillous surface. Results: Ultrastructurally, the bowel ep ithelium was well preserved in all animals. There were no objective ul trastrucrural differences between the controls and growth factor-expos ed animals. The mean villous-crypt ratio, mean number of villi per mil limeter of mucosa (cross section), and mean microvillous height were n ot significantly different among the groups. However, there was a subj ective increase in the number of lysosomes in the enterocytes exposed to EGF and IGF-1. Conclusions: Administration of EGF and IGF-1 after m assive small bowel resection does not appear to significantly alter th e small intestine epithelial ultrastructure when compared with the con trol group. The increase in lysosomes in some of the enterocytes of th e animals exposed to growth factors may be important because this find ing was not seen in any of the control electron photomicrographs. Stud ies to evaluate enterocyte gene and protein expression are necessary t o determine the mechanism of EGF and IGF-I enhancement of substrate ab sorption beyond intestinal adaptation. Copyright (C) 1997 by W.B. Saun ders Company.