Elsevier

Surgery

Volume 159, Issue 2, February 2016, Pages 548-559
Surgery

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

https://doi.org/10.1016/j.surg.2015.07.028Get rights and content

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.

Section snippets

Animals and operative procedure

The use of animals in this study was approved by the Animal Care Committee at Sun Yat-sen University (Guangzhou, China), and all animal experiments were conducted in accordance with the guidelines of the National Institutes of Health.

Adult, male, Sprague-Dawley rats weighing 230–280 g were used. The rats were housed in the departmental animal facility under normal (12 hours on/12 hours off) light/dark cycles and fasted overnight before the study but had free access to water. All animals were

Experiment 1: In vivo study

All animals survived the experimental period. There were no statistical differences in body weight or body temperature during the experiments among the groups (data not shown, P > .1).

Discussion

In the current study, we have shown that remifentanil preconditioning could improve intestinal morphologic changes, inhibits epithelial cell apoptosis, and confers intestinal protection without altering the hemodynamics and blood gas analysis in an in vivo rat model of I/R. Similarly in the IEC-6 cell culture model of OGD/R, remifentanil preconditioning increased IEC-6 cell viability as well as decreased the cell apoptosis after 4 hours of OGD followed by 4 hours of reintroduction of oxygen to

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    Supported by grants 81171847 and 81270456 (to Dr K.-X. Liu) as well as 81101407 (to Dr Y.-S. Li) from National Natural Science Foundation, Beijing, China.

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