title: Remifentanil preconditioning protects the small intestine against ischemia/reperfusion injury via intestinal δ- and μ-opioid receptors.
abstract: 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.
  
  
  CONCLUSIONS
  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.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Jian-Tong
authors.initials: JT
authors.lastname: Shen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Yun-Sheng
authors.initials: YS
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Zhi-Qiu
authors.initials: ZQ
authors.lastname: Xia
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Shi-Hong
authors.initials: SH
authors.lastname: Wen
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Xi
authors.initials: X
authors.lastname: Yao
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Wen-Jing
authors.initials: WJ
authors.lastname: Yang
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China.
authors.forename: Cai
authors.initials: C
authors.lastname: Li
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital, Sun Yat-sen University, Guangzhou, China. Electronic address: liukexuan705@163.com.
authors.forename: Ke-Xuan
authors.initials: KX
authors.lastname: Liu
mesh_terms: D000818:Animals; D017209:Apoptosis / Q000187:drug effects; D015415:Biomarkers / Q000378:metabolism; D002460:Cell Line; D002470:Cell Survival / Q000187:drug effects; D007413:Intestinal Mucosa / Q000098:blood supply / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D007421:Intestine, Small / Q000098:blood supply* / Q000187:drug effects / Q000378:metabolism / Q000473:pathology; D019194:Ischemic Preconditioning / Q000379:methods*; D008297:Male; D010880:Piperidines / Q000494:pharmacology / Q000627:therapeutic use*; D020011:Protective Agents / Q000494:pharmacology / Q000627:therapeutic use*; D011897:Random Allocation; D051381:Rats; D017207:Rats, Sprague-Dawley; D017465:Receptors, Opioid, delta / Q000037:antagonists & inhibitors / Q000378:metabolism*; D017473:Receptors, Opioid, kappa / Q000037:antagonists & inhibitors / Q000378:metabolism; D017450:Receptors, Opioid, mu / Q000037:antagonists & inhibitors / Q000378:metabolism*; D000077208:Remifentanil; D015427:Reperfusion Injury / Q000517:prevention & control*
chemical_list: D015415:Biomarkers; D010880:Piperidines; D020011:Protective Agents; D017465:Receptors, Opioid, delta; D017473:Receptors, Opioid, kappa; D017450:Receptors, Opioid, mu; D000077208:Remifentanil