Abstract
The present study was designed to determine whether glycogen synthase kinase-3β (GSK-3β) was involved in the cardioprotection by α7 nicotinic acetylcholine receptor (α7nAChR) agonist and limb remote ischemic postconditionings. Forty male Sprague-Dawley rats were randomly divided equally into control (C), α7nAChR agonist postconditioning (P), limb remote ischemic postconditioning (L), combined α7nAChR agonist and limb remote ischemic postconditioning (P+L) groups. At the end of experiment, serum cTnI, creatine kinase-MB (CK-MB), tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), high mobility group protein (HMGB1) and interleukin-10 (IL-10) levels were measured; infarct size (IS), myocardial expressions of GSK-3β, p-GSK-3β (Ser9), nuclear factor-κB (NF-κB) and p-NF-κB (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-α, IL-6 and HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) evidently decreased, and myocardial expression of p-GSK-3β (Ser9) obviously increased in groups P, L and P+L. Compared with group P, serum TNF-α, IL-6 and HMGB1 levels and myocardial expression of p-NF-κBp65 (Ser536) significantly increased, and myocardial expression of p-GSK-3β (Ser9) evidently decreased in group L. Compared with group L, serum TNF-α, IL-6, HMGB1 levels, and myocardial expression of p-NF-κBp65 (Ser536) significantly decreased, and myocardial expression of p-GSK-3β (Ser9) obviously increased in group P+L. In conclusion, our findings indicate that inhibition of GSK-3β to decrease NF-κB transcription is one of cardioprotective mechanisms of α7nAChR 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.