A rat model of ileal pouch-rectal anastomosis.
After colectomy and ileal pouch-rectal anastomosis, pouchitis may occur. Pouchitis is a poorly defined condition with unknown etiology. The aim of this study was to develop an animal model of pouchitis. Ileal pouch-rectal anastomosis was created in Lewis and Sprague-Dawley rats. Rats were studied 4 and 8 weeks after surgery, and pouchitis was assessed by stool output, histology, and tissue myeloperoxidase (MPO) levels. Some rats were treated with allopurinol or metronidazole beginning the day of surgery. Rats with pouches demonstrated inflammation with a monocytic infiltration, luminal exudate, mucosal ulcerations, and serosal inflammation. Rats with pouches had increased anaerobic bacterial flora compared with normal ileum. After creation of pouches, Lewis rats (histology score = 8.4 +/- 1.6; MPO = 17.3 +/- 3.6, mean +/- SD) developed more severe inflammation than Sprague-Dawley rats did (histology score = 4.3 +/- 1.8; MPO = 5.5 +/- 3.6) within 4 weeks, p < 0.001 and 8 weeks after surgery, p < 0.05. Stool output was also greater in Lewis (55 +/- 7 g/kg/day) compared with Sprague-Dawley rats with pouches (43 +/- 5 g/kg/day), p < 0.05. Metronidazole treatment reduced histology score (6.0 +/- 0.5) p < 0.05 and MPO (5.9 +/- 1.6) p < 0.001 in rats with pouches compared with rats with pouches that had no treatment. Allopurinol treatment in rats with pouches reduced histology score (4.0 +/- 1.7) and MPO (3.9 +/- 1.6), p < 0.001, compared with rats with pouches that had no treatment. Ileal pouch-rectal anastomosis in rats induced inflammation within 4 weeks, demonstrated differential host genetic susceptibility, and was associated with increased number of pouch bacteria. Anaerobes, especially bacteroides sp. and free radical, may mediate inflammation. Ileal pouch-rectal anastomosis surgery in rats may be a useful animal model for the study pouchitis.
Lichtman
S N
SN
Department of Pediatrics, University of North Carolina, Chapel Hill 27599-7220, USA.
Wang
J
J
Hummel
B
B
Lacey
S
S
Sartor
R B
RB
D000493:Allopurinol / Q000627:therapeutic use; D000818:Animals; D004195:Disease Models, Animal; D004353:Drug Evaluation, Preclinical; D005260:Female; D016166:Free Radical Scavengers / Q000627:therapeutic use; D008795:Metronidazole / Q000627:therapeutic use; D019449:Pouchitis / Q000188:drug therapy* / Q000276:immunology* / Q000473:pathology; D016737:Proctocolectomy, Restorative / Q000009:adverse effects / Q000379:methods*; D051381:Rats; D011917:Rats, Inbred Lew; D017207:Rats, Sprague-Dawley; D015203:Reproducibility of Results; D012720:Severity of Illness Index
D016166:Free Radical Scavengers; D008795:Metronidazole; D000493:Allopurinol