A Rat Model of Ischemic Enteritis: Pathogenic Importance of Enterobacteria, iNOS/NO, and COX-2/PGE2

Curr Pharm Des. 2017;23(27):4048-4056. doi: 10.2174/1381612823666170220154815.

Abstract

Background: We introduced a rat model of ischemic enteritis and investigated the roles of enterobacteria, Nitric Oxide (NO), and Prostaglandins (PGs) in its pathogenesis.

Methods: 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.

Results: 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.

Conclusion: 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.

Keywords: Ischemic enteritis; enterobacteria; nitric oxide; prostaglandin; rat; stenosis of the superior mesenteric artery.

Publication types

  • Review

MeSH terms

  • Animals
  • Cyclooxygenase 2 / metabolism
  • Dinoprostone / metabolism
  • Disease Models, Animal
  • Enteritis / microbiology
  • Enteritis / physiopathology*
  • Enterobacteriaceae / isolation & purification
  • Enterobacteriaceae Infections / complications*
  • Humans
  • Ischemia / complications
  • Male
  • Nitric Oxide / metabolism*
  • Nitric Oxide Synthase Type II / metabolism
  • Rats
  • Receptors, Prostaglandin E, EP4 Subtype / metabolism

Substances

  • Receptors, Prostaglandin E, EP4 Subtype
  • Nitric Oxide
  • Nitric Oxide Synthase Type II
  • Cyclooxygenase 2
  • Dinoprostone