title: Diabetes mellitus abrogates the cardioprotection of sufentanil against ischaemia/reperfusion injury by altering glycogen synthase kinase-3β.
abstract: BACKGROUND
  Sufentanil is widely used in clinical anaesthesia because of its protective effects against ischaemia/reperfusion injury. Diabetes mellitus elevates the activity of glycogen synthase kinase-3β (GSK-3β), thereby increasing the permeability of mitochondrial transition pore. This study investigated the role of GSK-3β in ameliorating the cardioprotective effect of sufentanil post-conditioning in diabetic rats.
  
  
  METHODS
  Streptozotocin-induced diabetic rats and age-matched non-diabetic rats were subjected to 30 min of ischaemia and 120 min of reperfusion. Five minutes before reperfusion, rats were administered one of the following: a vehicle, sufentanil (1 μg/kg), or a GSK-3β inhibitor SB216763 (0.6 mg/kg). Myocardial infarct size, cardiac troponin I, and the activity of GSK-3β were then assessed.
  
  
  RESULTS
  Sufentanil post-conditioning significantly reduced myocardial infarct size in the non-diabetic, but not in diabetic rats. SB216763 reduced infarct size in both diabetic and non-diabetic animals. Sufentanil-induced phospho-GSK-3β was reduced 5 min after reperfusion in diabetic rats, but not in non-diabetic rats.
  
  
  CONCLUSIONS
  Sufentanil treatment was ineffective in preventing against ischaemia/reperfusion in diabetic rats, which is associated with the activation of GSK-3β. Our results also suggest that direct inhibition of GSK-3β may provide a strategy to protect diabetic hearts against ischaemia/reperfusion injury.
authors.affiliation: Department of Anesthesiology, The First Affiliated Hospital of Anhui Medical University, Hefei, China.
authors.forename: Q L
authors.initials: QL
authors.lastname: Chen
authors.forename: E W
authors.initials: EW
authors.lastname: Gu
authors.forename: L
authors.initials: L
authors.lastname: Zhang
authors.forename: Y Y
authors.initials: YY
authors.lastname: Cao
authors.forename: Y
authors.initials: Y
authors.lastname: Zhu
authors.forename: W P
authors.initials: WP
authors.lastname: Fang
mesh_terms: D018686:Anesthetics, Intravenous / Q000494:pharmacology / Q000627:therapeutic use*; D000818:Animals; D001794:Blood Pressure / Q000187:drug effects; D015153:Blotting, Western; D002316:Cardiotonic Agents; D003921:Diabetes Mellitus, Experimental / Q000201:enzymology / Q000503:physiopathology*; D004562:Electrocardiography; D004791:Enzyme Inhibitors / Q000494:pharmacology; D038362:Glycogen Synthase Kinase 3 / Q000378:metabolism*; D006339:Heart Rate / Q000187:drug effects; D007211:Indoles / Q000494:pharmacology; D008297:Male; D008301:Maleimides / Q000494:pharmacology; D009203:Myocardial Infarction / Q000473:pathology; D009206:Myocardium / Q000473:pathology; D009929:Organ Size; D051381:Rats; D017207:Rats, Sprague-Dawley; D015427:Reperfusion Injury / Q000503:physiopathology* / Q000517:prevention & control*; D017409:Sufentanil / Q000494:pharmacology / Q000627:therapeutic use*; D019210:Troponin I / Q000378:metabolism
chemical_list: D018686:Anesthetics, Intravenous; D002316:Cardiotonic Agents; D004791:Enzyme Inhibitors; D007211:Indoles; D008301:Maleimides; C417521:SB 216763; D019210:Troponin I; D017409:Sufentanil; D038362:Glycogen Synthase Kinase 3