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Acta Physiologica 2009; Volume 195, Supplement 670
Belgian Society for Fundamental and Clinical Physiology and Pharmacology, Spring Meeting 2009
3/7/2009-3/7/2009
Ghent University, Gent, Belgium
OPTIMALISATION OF THE TIME COURSE OF TNBS COLITIS IN THE RAT: A MODEL FOR POSTINFLAMMATORY DYSFUNCTIONS
Abstract number: P-04
Vermeulen1 W., De Man1 J.G., Ruyssers1 N.E., De Schepper1 H.U., Van den Bossche2 R.M., Pelckmans1 P.A., De Winter1 B.Y.
1Laboratory of Experimental Medicine and Pediatrics, Division of Gastroenterology, Faculty of Medicine
2Laboratory of Pharmacology, Faculty of Pharmaceutical, Biomedical and Veterinary Sciences, University of Antwerp, Universiteitsplein 1, 2610 Antwerp, Belgium.
In the gastrointestinal wall, inflammation can induce long-lasting alterations in visceral sensation and bowel motility even when overt signs of acute inflammation have subsided. This is clinically documented in patients suffering from chronic inflammatory bowel diseases in remission and patients suffering from postinflammatory irritable bowel syndrome. Although the modulating role of intestinal inflammation in these disorders is acknowledged, validated animal models for the investigation of the underlying pathophysiological mechanisms are scarce.
The aim of this study was to optimise a postinflammatory animal model to study the pathophysiological mechanisms involved in the occurrence of motility and sensitivity disorders following an episode of acute colitis.
Colitis was chemically induced in female Wistar rats (180200 g; n at least 10 per group) by intracolonic instillation of 7.5 mg trinitrobenzene sulphonic acid (TNBS) in 30% ethanol. Control rats received a saline instillation. To explore the TNBS-induced colonic inflammatory response in a time-dependent manner, rats were sacrificed respectively 3 days, 1 week, 2 and 4 weeks after TNBS administration. Inflammation was assessed by a macroscopic (010) and microscopic (06) score next to a myeloperoxidase (MPO) assay.
Intracolonic instillation of TNBS induced an acute and mild colonic inflammation within 3 days, which was characterized macroscopically by hyperaemia, oedema, ulceration and limited necrosis with a median macroscopic score of 4 (26). Histological examination of the inflamed region showed thickening and oedema of the submucosa, localized ulceration and infiltration of inflammatory cells resulting in a median microscopic score of 3 (14). Colonic MPO levels increased from 0.3 0.1 U/g in controls to 10.5 3.2 U/g 3 days after TNBS instillation (p < 0.05). One week after TNBS, the median macroscopic damage score was 0 (02) and the median histological score was 0 (02). However, the MPO level was still elevated to 10.3 4.6 U/g compared to 1.1 0.3 U/g in controls (p < 0.05) indicating that an inflammatory infiltrate was still present. Two weeks after TNBS instillation, inflammation subsided completely macroscopically, whereas some rats still showed minor inflammatory changes on histological sections (median damage score of 0 (01)). Colonic MPO content remained elevated to 4.5 2.7 U/g compared to 1.3 0.4 U/g in controls. Four weeks after colitis induction, no significant differences between saline- and TNBS-treated animals remained, illustrating complete resolution of the TNBS-induced inflammation.
These data demonstrate that a single dose of 7,5 mg TNBS dissolved in 30% ethanol resulted into a colitis which is transient and self-limiting within 4 weeks. It should be noted that optimising and evaluating postinflammatory conditions is the first step in the development of an animal model that mimics pathophysiological symptoms as seen in postinflammatory bowel diseases.
To cite this abstract, please use the following information:
Acta Physiologica 2009; Volume 195, Supplement 670 :P-04