The blood flow restoration of ischemic tissues causes myocardial injury. Dexmedetomidine (Dex) protects multi-organs against ischemia/reperfusion (I/R) injury. This study investigated the protective mechanism of Dex post-treatment in myocardial I/R injury. The rat model of myocardial I/R was established. The effects of Dex post-treatment on cardiac function and autophagy flow were observed. Dex attenuated myocardial I/R injury and reduced I/R-induced autophagy in rats. Dex weakened the interactions between Beclin1 and Vps34 and Beclin1 and Atg14L, thus downregulating Vps34 kinase activity. In vitro, the cardiomyocytes subjected to oxygen glucose deprivation/reoxygenation were treated with Dex and PI3K inhibitor LY294002. LY294002 attenuated the myocardial protective effect of DEX, indicating that Dex protected against cardiac I/R by activating the PI3K/Akt pathway. In conclusion, Dex upregulated the phosphorylation of Beclin1 at S295 site by activating the PI3K/Akt pathway and reduced the interactions of Atg14L-Beclin1-Vps34 complex, thus inhibiting autophagy and protecting against myocardial I/R injury.
Keywords: Autophagy; Beclin1; Dexmedetomidine; Ischemia/reperfusion; LY294002; Myocardium; PI3K/Akt pathway; Vps34.
© 2021. The Author(s), under exclusive licence to Springer Science+Business Media, LLC, part of Springer Nature.