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Diabetes mellitus abrogates the cardioprotection of sufentanil against ischaemia/reperfusion injury by altering glycogen synthase kinase‐3β
Author(s) -
CHEN Q. L.,
GU E. W.,
ZHANG L.,
CAO Y. Y.,
ZHU Y.,
FANG W. P.
Publication year - 2013
Publication title -
acta anaesthesiologica scandinavica
Language(s) - English
Resource type - Journals
SCImago Journal Rank - 0.738
H-Index - 107
eISSN - 1399-6576
pISSN - 0001-5172
DOI - 10.1111/j.1399-6576.2012.02748.x
Subject(s) - medicine , sufentanil , cardioprotection , diabetes mellitus , ischemia , streptozotocin , reperfusion injury , mitochondrial permeability transition pore , anesthesia , glycogen , pharmacology , endocrinology , apoptosis , programmed cell death , biochemistry , chemistry
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 SB 216763 (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.