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, stenosis of the superior mesenteric artery, enterobacteria, nitric oxide, prostaglandin, rat.
Current Pharmaceutical Design
Title:A Rat Model of Ischemic Enteritis: Pathogenic Importance of Enterobacteria, iNOS/NO, and COX-2/PGE2
Volume: 23 Issue: 27
Author(s): Koji Takeuchi*, Yoshino Komatsu, Yuka Nakamori and Tohru Kotani
Affiliation:
- General Incorporated Association, Kyoto Research Center for Gastrointestinal Diseases, Karasuma- Oike, 671, Kyoto 604-8106,Japan
Keywords: Ischemic enteritis, stenosis of the superior mesenteric artery, enterobacteria, nitric oxide, prostaglandin, rat.
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.
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Cite this article as:
Takeuchi Koji*, Komatsu Yoshino, Nakamori Yuka and Kotani Tohru, A Rat Model of Ischemic Enteritis: Pathogenic Importance of Enterobacteria, iNOS/NO, and COX-2/PGE2, Current Pharmaceutical Design 2017; 23 (27) . https://dx.doi.org/10.2174/1381612823666170220154815
DOI https://dx.doi.org/10.2174/1381612823666170220154815 |
Print ISSN 1381-6128 |
Publisher Name Bentham Science Publisher |
Online ISSN 1873-4286 |
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