title: A Rat Model of Ischemic Enteritis: Pathogenic Importance of Enterobacteria, iNOS/NO, and COX-2/PGE2.
abstract: We introduced a rat model of ischemic enteritis and investigated the roles of enterobacteria, Nitric Oxide (NO), and Prostaglandins (PGs) in its pathogenesis.
  
  
  
  Male rats were used after 18 h of fasting. Ischemic enteritis was induced by partial ligation of the superior mesenteric artery (SMA). Under ether anesthesia, SMA was isolated, and a stenosis was made by placing a needle (23 guage) on the vessel and ligating both the vessel and needle, and then a needle was removed from the ligature. Animals were then fed normally after surgery. Various drugs such as antibiotics, cyclooxygenase (COX) inhibitors, NO synthase (NOS) inhibitors and PGE2 were administered for 2 days after surgery.
  
  
  
  Stenosis of the SMA caused mucosal ischemia and damaged the small intestine, particularly the ileum, within 3 days. The development of enteritis was accompanied by mucosal invasion of enterobacteria, with the bacterial count being significantly increased 8 h after surgery. The severity of enteritis was prevented by the prior administration of ampicillin, L-NAME, or aminoguanidine, but aggravated by that of indomethacin or rofecoxib. The deleterious effects of indomethacin were antagonized by the co-administration of PGE2; these effects were mimicked by AE1-329, an EP4 agonist, and abrogated by AE3-208, an EP4 antagonist. The expression of iNOS and COX-2 was up-regulated in the small intestine in a time-dependent manner after ischemia caused by stenosis of the SMA, with increases in the mucosal contents of NO and PGE2.
  
  
  
  These results suggest that enterobacteria played a major pathogenic role in this model of ischemic enteritis, and that iNOS/NO was deleterious in the pathogenesis of these lesions, while COX-2/PGE2 prevented the development of ischemic enteritis by activating EP4 receptors.
authors.affiliation: General Incorporated Association, Kyoto Research Center for Gastrointestinal Diseases, Karasuma- Oike, 671, Kyoto 604-8106. Japan.
authors.forename: Koji
authors.initials: K
authors.lastname: Takeuchi
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414. Japan.
authors.forename: Yoshino
authors.initials: Y
authors.lastname: Komatsu
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414. Japan.
authors.forename: Yuka
authors.initials: Y
authors.lastname: Nakamori
authors.affiliation: Division of Pathological Sciences, Department of Pharmacology and Experimental Therapeutics, Kyoto Pharmaceutical University, Yamashina, Kyoto 607-8414. Japan.
authors.forename: Tohru
authors.initials: T
authors.lastname: Kotani
mesh_terms: D000818:Animals; D051546:Cyclooxygenase 2 / Q000378:metabolism; D015232:Dinoprostone / Q000378:metabolism; D004195:Disease Models, Animal; D004751:Enteritis / Q000382:microbiology / Q000503:physiopathology*; D004755:Enterobacteriaceae / Q000302:isolation & purification; D004756:Enterobacteriaceae Infections / Q000150:complications*; D006801:Humans; D007511:Ischemia / Q000150:complications; D008297:Male; D009569:Nitric Oxide / Q000378:metabolism*; D052247:Nitric Oxide Synthase Type II / Q000378:metabolism; D051381:Rats; D058309:Receptors, Prostaglandin E, EP4 Subtype / Q000378:metabolism
chemical_list: D058309:Receptors, Prostaglandin E, EP4 Subtype; D009569:Nitric Oxide; D052247:Nitric Oxide Synthase Type II; D051546:Cyclooxygenase 2; D015232:Dinoprostone
keywords: Ischemic enteritis; enterobacteria; nitric oxide; prostaglandin; rat; stenosis of the superior mesenteric artery