Diabetes mellitus abrogates the cardioprotection of sufentanil against ischaemia/reperfusion injury by altering glycogen synthase kinase-3β

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-3 beta (GSK-3 beta), thereby increasing the permeability of mitochondrial transition pore. This study investigated the role of GSK-3 beta 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?mu g/kg), or a GSK-3 beta inhibitor SB216763 (0.6?mg/kg). Myocardial infarct size, cardiac troponin I, and the activity of GSK-3 beta 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-3 beta 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-3 beta. Our results also suggest that direct inhibition of GSK-3 beta may provide a strategy to protect diabetic hearts against ischaemia/reperfusion injury.