Development of a total colectomy and ileorectal anastomosis rat model to evaluate colonic metaplasia

Abstract

Background Ulcerative colitis (UC) is an idiopathic inflammatory condition of the colon that may require surgical intervention including proctocolectomy and either ileal pouch-anal anastomosis (IPAA) or in the pediatric population, low ileorectal anastomosis (IRA). Often, subsequent physiologic alteration (or colonic metaplasia) occurs in the anastomosed small bowel that includes changes in mucin content, villous blunting, and increased expression of WNT5A, a marker of colonic crypt regeneration. We developed a rat low IRA model to assess and study the development of colonic metaplasia. Materials and methods We subjected male Sprague-Dawley rats (n=17) to total colectomy and low IRA surgery and evaluated healing periodically by endoscopic evaluation. The ileum upstream of the anastomosis was assessed by hematoxylin and eosin (H&E) staining and the mucin content was measured by high iron diamine-Alcian blue (HID-AB) staining. Wnt5a transcripts were quantified by RT-qPCR at the 8 week study endpoint. Results Although no gross endoscopic evidence of inflammation was seen throughout the course of the study, colonic metaplasia in the small bowel was detected in 7 out of 10 (70%) rats at the study endpoint. In rats with colonic metaplasia, enhanced expression of Wnt5a was evident at the study endpoint compared to levels in the terminal ileum at the time of surgery. Conclusions Within 4–8 weeks, the majority of rats subjected to IRA developed colonic metaplasia defined by villous blunting, changes in mucin content, and increased expression of Wnt5a. This model provides a method to study small bowel colonic metaplasia.

Inflammatory bowel disease-specific findings are common morphological changes in the ileal pouch with ulcerative colitis

“…The increase in the number of neutrophils and other inflammatory cells in the lamina propria may increase the cell density in the lamina propria, and the thickening of the lamina propria associated with this increase may result in crypt hyperplasia. Colonic metaplasia including www.nature.com/scientificreports/ crypt hyperplasia and villus atrophy seems to be a non-IBD specific finding, as it is also seen in the intestinal mucosa of celiac disease in Marsh type 3 29 and in the ileal pouch of normal mice 30 .…”

Arterial supply to the rat colon

“…In the field of gastrointestinal research, the rat colon is widely used to study procedures that require total or partial colectomy including transplantation (Galvão et al., 2006; Zhou et al., 2006), laparoscopic resection (Durães et al., 2013), ulcerative colitis (Schieffer et al., 2017) and anastomosis healing (Akyuz et al., 2018; Boersema et al., 2016; Ghiselli et al., 2020). As these procedures may induce ischaemia and leakage of the anastomosis (Akyuz et al., 2018; Boersema et al., 2016), detailed knowledge of the arterial anatomy is important for accurate and reproducible surgery and to avoid complications.…”