Conclusion
Dex suppressed oxidative stress and inflammation by promoting autophagy through activating the AMPK/SIRT3 pathway, thus protecting the heart against the I/R injury.
Methods
H9c2 cells were treated with Dex (1 μM) for 24 h followed by oxygen-glucose deprivation/re-oxygenation (OGD/R). ANP and BNP mRNA of H9c2 cells and the LDH release were measured. Apoptosis of H9c2 cells was analyzed by flow cytometry. Mitochondrial membrane potential and superoxide production were detected by JC-1 staining and MitoSOXTM Red, respectively. Cell aerobic respiration was measured using Seahorse analysis. In vivo, mice were injected with Dex (25 μg/kg, i.p., once daily) for 5 days and then subjected to heart I/R. Heart function was analyzed by echocardiography. CK-MB and LDH were measured by Elisa. Infarct size was measured using TTC-Evans blue staining. Mitochondrial ultrastructure was observed using transmission electron microscopy. DHE staining, SOD activity, the content of MDA, and the content of GSH/GSSG of heart were measured to evaluate the oxidative stress. In addition, inflammatory cytokines were measured in vivo and in vitro. Furthermore, AMPK, SIRT3, and autophagy-related protein expression in the heart were detected by Western blot.
Objective
Myocardial ischemia-reperfusion (I/R) injury is a detrimental disease, resulting in high morbidity and mortality globally. In this study, we aimed to investigate the role of Dex in mitigating cardiac I/R injury.
Results
Dex reduced the H9c2 cells injury exposed to OGD/R, accompanied by improved mitochondrial function and membrane potential. In vivo, Dex improved heart function, myocardial injury, and the mitochondria ultrastructure following I/R injury. Meanwhile, Dex inhibited myocardial oxidative stress and inflammation in the myocardial I/R. Furthermore, Compound C (an AMPK inhibitor) could inhibit Dex-induced autophagy in the I/R heart and the 3-MA (an autophagy inhibitor) could partially interfere with the effects of Dex on the protection of I/R heart.