Inhibition of glycogen synthase kinase-3β is involved in cardioprotection by α7nAChR agonist and limb remote ischemic postconditionings

The present study was designed to determine whether glycogen synthase kinase-3 beta (GSK-3 ss) was involved in the cardioprotection by alpha 7 nicotinic acetylcholine receptor (alpha 7nAChR) agonist and limb remote ischemic postconditionings. Forty male Sprague-Dawley rats were randomly divided equally into control (C), alpha 7nAChR agonist postconditioning (P), limb remote ischemic postconditioning (L), combined alpha 7nAChR agonist and limb remote ischemic postconditioning (P+L) groups. At the end of experiment, serum cTnI, creatine kinase-MB (CK-MB), tumor necrosis factor-alpha (TNF-alpha), interleukin-6 (IL-6), high mobility group protein (HMGB1) and interleukin-10 (IL-10) levels were measured; infarct size (IS), myocardial expressions of GSK-3 beta, p-GSK-3 beta (Ser9), nuclear factor-kappa B (NF-kappa B) and p-NF-kappa B (Ser536) in the ischemic area were assessed. The results showed that compared with group C, IS, serum cTnI and CK-MB levels obviously decreased in groups P, L and P+ L. Compared with groups P and L, IS, serum cTnI and CK-MB levels significantly decreased in group P+ L. Compared with group C, serum TNF-alpha, IL-6 and HMGB1 levels, and myocardial expression of p-NF-kappa Bp65 (Ser536) evidently decreased, and myocardial expression of p-GSK-3 beta (Ser9) obviously increased in groups P, L and P+ L. Compared with group P, serum TNF-alpha, IL-6 and HMGB1 levels and myocardial expression of p-NF-kappa Bp65 (Ser536) significantly increased, and myocardial expression of p-GSK-3 beta (Ser9) evidently decreased in group L. Compared with group L, serum TNF-alpha, IL-6, HMGB1 levels, and myocardial expression of p-NF-kappa Bp65 (Ser536) significantly decreased, and myocardial expression of p-GSK-3 beta (Ser9) obviously increased in group P+ L. In conclusion, our findings indicate that inhibition of GSK-3 beta to decrease NF-kappa B transcription is one of cardioprotective mechanisms of alpha 7nAChR agonist and limb remote ischemic postconditionings by anti-inflammation, but improved cardioprotection by combined two interventions is not completely attributable to an enhanced anti-inflammatory mechanism.