Remifentanil preconditioning protects the small intestine against ischemia/reperfusion injury via intestinal δ- and μ-opioid receptors

Background Intestinal ischemia/reperfusion (I/R) injury can cause a high rate of mortality in the perioperative period. Remifentanil has been reported to provide protection for organs against I/R injury. We hypothesized that remifentanil preconditioning would attenuate the small intestinal injury induced by intestinal I/R. Methods We used both an in vivo rat model of intestinal I/R injury and a cell culture model using IEC-6 cells (the rat intestinal epithelial cell line) subjected to oxygen and glucose deprivation (OGD). Remifentanil was administered before ischemia or OGD, and 3 specific opioid receptors antagonists, naltrindole (a δ-OR selective antagonist), nor-binaltorphimine (nor-BNI, a κ-OR selective antagonist), and CTOP (a μ-OR selective antagonist), were administered before preconditioning to determine the role of opioid receptors in the intestinal protection mediated by remifentanil. Results In the in vivo rat model, intestinal I/R induced obvious intestinal injury as evidenced by increases in the Chiu score, serum diamine oxidase activity, the apoptosis index, and the level of cleaved caspase-3 protein expression, whereas remifentanil preconditioning significantly improved these changes in vivo. In the in vitro cell culture exposed to OGD, cell viability (MTT, ie, (3-[4,5-dimethylthiazol-2-yl]-2,5 diphenyl tetrazolium bromide) assay and flow cytometric analysis showed that remifentanil preconditioning enhanced IEC-6 cell viability and decreased apoptosis. In both in vitro and in vivo models, the aforementioned protective effects of remifentanil preconditioning were abolished completely by previous administration of the δ- or μ-opioid markedly attentuated but not the κ-opioid receptor antagonist. Conclusion Remifentanil preconditioning appears to act via δ- and μ-opioid receptors to protect the small intestine from intestinal I/R injury by attenuating apoptosis of the intestinal mucosal epithelial cells.