Abstract
Purpose: Diabetes mellitus as a main
risk-factor of ischemic heart disease may interfere with
postconditioning’scardioprotective effects. This study aimed to investigate the
involvement of glycogen synthase kinase-3β (GSK-3β) and oxidation status in
chronic diabetes-induced loss of cardioprotective effect of
ischemic-postconditioning (IPostC) in Wistar rats.
Methods: After 8 weeks of induction of diabetes by
streptozotocin (50mg/kg), hearts of control and diabetic rats were isolated and
mounted on a constant-pressure Langendorff system. All hearts were subjected to
30min regional ischemia followed by 60min reperfusion (by occluding and
re-opening of left anterior descending coronary artery, respectively). IPostC
was applied immediately at the onset of reperfusion. At the end of
reperfusion, the infarct size of
myocardium was measured via computerized planimetry. Myocardial contents of
malondealdehyde and glutathione as indices of oxidative status were assayed spectrophotometrically
and the total and phosphorylated forms of myocardial GSK-3β were quantified through western blotting.
Results: IPostC reduced the infarct size of control hearts from
41±2.9% to 28±1.9% (P<0.05), whereas it could not induce significant changes
in infarct size of diabetic animals (35±1.8% vs. 39±3.1%). IPostC-induced
reduction in malondealdehyde and elevation in glutathione contents were
significant only in control not in diabetic hearts. The total forms of GSK-3β
were similar in all groups; however, the phosphorylation of GSK-3β (at Ser9) by
IPostC was greater in control hearts than diabetics (P<0.01).
Conclusion: The failure of
cardioprotection by IPostC in diabetic hearts may be attributed to the loss of
phosphorylation of GSK-3β and thereby increase in oxidative stress in diabetic
states.