Effect of Transforming Growth Factor- on Intestinal Adaptation in a Rat Model of Short Bowel Syndrome Igor Sukhotnik, M.D.,* Evgeny Yakirevich, M.D., D.Sc.,* Arnold G. Coran, M.D.,† Leonardo Siplovich, M.D.,* Michael Krausz, M.D.,‡ Mark Hirsh, M.D.,‡ Edmund Sabo, M.D.,* and Eitan Shiloni, M.D.* *Rappaport Faculty of Medicine, Technion, Carmel Medical Center, Haifa 34362, Israel; and ‡Rambam Medical Center, Haifa, Israel; and †Section of Pediatric Surgery, University of Michigan Medical School and C. S. Mott Children’s Hospital, Ann Arbor, Michigan Submitted for publication April 8, 2002 Objective. TGF- has recently been shown to stimu- late enterocyte proliferation. In the present study we investigated the effect of TGF- on enterocyte prolif- eration and loss via apoptosis and its effects on intes- tinal adaptation in a rat following massive bowel re- section. Methods. Male Sprague–Dawley rats underwent bowel transection and reanastomosis (sham group) or 75% small bowel resection and anastomosis (SBS group) and were treated with intraperitoneal TGF- (75 g/kg) from the ninth postoperative day (SBS– TGF- group). Parameters of intestinal adaptation (overall bowel and mucosal weight, mucosal DNA and protein, villus height, and crypt depth), enterocyte proliferation, and apoptosis were determined on day 15. Statistical significance was determined by ANOVA with a P < 0.05 considered significant. Results. SBS–TGF- rats demonstrated a significant increase (vs SBS) in duodenal, jejunal, and ileal over- all bowel and mucosal weights; ileal mucosal DNA and protein; and jejunal and ileal villus height. SBS–TGF- rats also showed an increased cell proliferation index in jejunum (704  43 vs 499  63 BrdU-positive cells/10 crypts, P < 0.05) and ileum (715  84 vs 529  40 BrdU-positive cells/10 crypts, P < 0.05) and decreased apoptotic index in ileum (8.7  1.1 vs 21.8  3.2 apo- ptotic cells/1000 villus cells, P < 0.05) compared to SBS animals. Conclusions. In a rat model of SBS, TGF- enhances intestinal adaptation. Possible mechanisms may in- clude increased cell proliferation and decreased en- terocyte loss via apoptosis. © 2002 Elsevier Science (USA) Key Words: short bowel syndrome; intestinal adapta- tion; transforming growth factor-. INTRODUCTION Short bowel syndrome (SBS) is a clinical condition characterized by nutrient malabsorption because of de- creased intestinal length or competence, resulting in reduced growth and development in the growing child. Many clinical conditions in the neonate may necessi- tate intestinal resection; however, the most common causes are necrotizing enterocolitis, intestinal atresia, and volvulus [1]. With improvement in neonatal inten- sive care and a higher survival rate of premature ba- bies, the incidence of necrotizing enterocolitis and, therefore, the incidence of short bowel syndrome have increased [2]. Because of drastic loss of absorptive sur- face area and concomitant decrease in digestive en- zymes and transport proteins, massive small bowel resection leads to malabsorption of nutrients and mi- cronutrients and to water and electrolyte losses [3]. Therefore, the patients with short bowel syndrome usually require artificial nutrition after operation. To- tal parenteral nutrition (TPN) is initiated usually as soon as clinical stability allows. TPN provides ade- quate total caloric intake and necessary amounts of nutrients and micronutrients and, finally, it also “buys time” for gradual tolerance of enteral feedings and successful adaptation of the intestine [4]. However, the key to survival after massive small bowel resection is the ability of the residual bowel to adapt. Adaptation is the term that is applied to the progressive recovery from intestinal failure, resulting in increased absorp- tive surface area (structural adaptation) and increased nutrient absorption by isolated enterocytes (functional absorption) [5, 6]. Over the past decades, much research has focused on the question of which factors may be trophic for gut Journal of Surgical Research 108, 235–242 (2002) doi:10.1006/jsre.2002.6556 235 0022-4804/02 $35.00 © 2002 Elsevier Science (USA) All rights reserved.