Recovery of ischaemic injured porcine ileum: evidence for a contributory role of COX-1 and COX-2

摘要

Background: We have previously shown that the non-selective cyclooxygenase (COX) inhibitor indomethacin retards recovery of intestinal barrier function in ischaemic injured porcine ileum. However, the relative role of COX-1 and COX-2 elaborated prostaglandins in this process is unclear.Aims: To assess the role of COX-1 and COX-2 elaborated prostaglandins in the recovery of intestinal barrier function by evaluating the effects of selective COX-1 and COX-2 inhibitors on mucosal recovery and eicosanoid production.Methods: Porcine ileal mucosa subjected to 45 minutes of ischaemia was mounted in Ussing chambers, and transepithelial electrical resistance was used as an indicator of mucosal recovery. Prostaglandins E1 and E2 (PGE) and 6-keto-PGF1α (the stable metabolite of prostaglandin I2 (PGI2)) were measured using ELISA. Thromboxane B2 (TXB2, the stable metabolite of TXA2) was measured as a likely indicator of COX-1 activity.Results: Ischaemic injured tissues recovered to control levels of resistance within three hours whereas tissues treated with indomethacin (5×10⁻⁶ M) failed to fully recover, associated with inhibition of eicosanoid production. Injured tissues treated with the selective COX-1 inhibitor SC-560 (5×10⁻⁶ M) or the COX-2 inhibitor NS-398 (5×10⁻⁶ M) recovered to control levels of resistance within three hours, associated with significant elevations of PGE and 6-keto-PGF1α compared with untreated tissues. However, SC-560 significantly inhibited TXB2 production whereas NS-398 had no effect on this eicosanoid, indicating differential actions of these inhibitors related to their COX selectivity.Conclusions: The results suggest that recovery of resistance is triggered by PGE and PGI2, which may be elaborated by either COX-1 or COX-2.