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.