OBJECTIVE To investigate the effects of dexmedetomidine (DEX) on the hypoxia/reoxygenation (H/R) injury of cardiomyocytes and the P62/Keap1/Nrf2 signaling pathway.

METHODS H9c2 cells were cultured, and then treated with 1, 2.5, 5, 10 and 20 μmol/L dexmedetomidine for 24 h, respectively. After H/R treatment, the cell viability of each group was detected by CCK-8, and suitable concentrations were screened for subsequent experiments. H9c2 cells were separated into Control group, H/R group, DEX-L group, DEX-M group, DEX-H group, and DEX-H+ML385 (Nrf2 inhibitor) group. ELISA was applied to detect the injury markers and oxidative stress levels in cardiomyocytes. Flow cytometry was applied to detect the apoptosis of cardiomyocytes. Western blot was applied to detect the expression level of P62/Keap1/Nrf2 signaling pathway related proteins and autophagic proteins.

RESULTS The levels of CK-MB, LDH, MDA, apoptosis rate, and the expression of Bax, LC3II/LC3I, and Beclin-1 in the H/R group were higher than those in the Control group, while the level of SOD and the expressions of Bcl-2, P62, Keap1, Nrf2, and HO-1 were lower (P<0.05). DEX treatment decreased the levels of CK-MB, LDH, MDA levels and apoptosis rate, Bax, LC3II/LC3I, and Beclin-1 expression, and increased the SOD level and Bcl-2, P62, Keap1, Nrf2, and HO-1 expressions (P<0.05). ML385 treatment partially reversed the ameliorating effect of DEX on the H/R injury of cardiomyocytes (P<0.05).

CONCLUSION Dexmedetomidine improves the H/R injury of cardiomyocytes, and its mechanism of action is related to the activation of the P62/Keap1/Nrf2 signaling pathway.