GSK-3β inhibition confers cardioprotection associated with the restoration of mitochondrial function and suppression of endoplasmic reticulum stress in sevoflurane preconditioned rats following ischemia/reperfusion injury

Background:Sevoflurane has been shown to protect against myocardial ischemia/reperfusion (I/R) injury in animals, while its cardioprotection is lost if the ischemic insult is too long. In this study, we proposed a prevailing hypothesis that GSK-3β inhibitor-mediated activation of GSK-3β/β-catenin signaling pathway provides additional cardioprotection in sevoflurane preconditioned rats following I/R injury.Methods:Rats were subjected to treatment with TDZD-8, a GSK-3β inhibitor, 5 minutes prior to sevoflurane preconditioning and 30-minute ischemia and 120-minute reperfusion. Furthermore, in order to find out whether this cardioprotection is linked with mitochondrial function and endoplasmic reticulum stress (ERS), we isolated mitochondria from rat hearts perfused with TDZD-8 and determined the alternations of ERS markers.Results:Sevoflurane preconditioning or GSK-3β inhibitor treatment prevented cardiomyocyte apoptosis, phosphorylated GSK-3β and accelerated total β-catenin expression levels, reduced mitoch...