Abstract
BACKGROUND: Currently there is no an appropriate model to study intestinal mucosal atrophy in vivo that preserves the nutritional status of the organism. MATERIALS AND METHODS: We created a defunctionalized segment of jejunum via a dead-end Roux-en-Y anastomosis in rats. We compared tissue morphometric parameters in the intestinal mucosa of the defunctionalized bowel with that of the mucosa proximal and distal to the anastomosis. We further measured extracellular signal-regulated kinase (ERK) activation within the mucosa as well as sucrase-isomaltase and dipeptidyl peptidase-4 levels as markers of intestinal mucosal differentiation by Western blotting of mucosal scrapings. RESULTS: Three days after anastomosis, the defunctionalized bowel exhibited decreased diameter and thickness of both the mucosa and the fibromuscular layer compared with adjacent bowel in continuity for luminal nutrient flow or with bowel from control animals. Sucrase-isomaltase and dipeptidyl peptidase-4 levels also were decreased. Furthermore, mucosal ERK activation, assessed as the ratio of phosphorylated to total ERK, also was reduced. Animal weights did not differ between bypassed and control animals. CONCLUSIONS: Deprivation of nutrient flow in a segment of bowel by defunctionalizing Roux-en-anastomosis produces mucosal atrophy as indicated by altered histology, differentiation marker expression, and ERK signaling, in animals that are otherwise able to maintain enteral nutrition.