Protective effect of dexmedetomidine on neuronal hypoxic injury through inhibition of miR-134

Objective: To explore the mechanism of dexmedetomidine (DEX)-mediated miR-134 inhibition in hypoxia-induced damage in PC12 cells.

Methods: Hydrogen peroxide (H₂O₂)-stimulated PC12 cells were divided into control, H₂O₂, DEX + H₂O₂, miR-NC/inhibitor + H₂O₂, and miR-NC/ mimic + DEX + H₂O₂ groups. Cell viability and Apoptosis were assessed by the 3-(4,5-dimethylthiazol(-2-y1)-2,5-diphenytetrazolium bromide (MTT) assay and Annexin V-FITC/PI staining, while gene and protein expression levels were detected by qRT-PCR and western blotting. Reactive Oxygen Species (ROS) levels were tested by 2',7'-dichlorodihydrofluorescein diacetate (DCFH-DA) staining, and malondialdehyde (MDA) content was determined with a detection kit.

Results: DEX treatment decreased H₂O₂-elevated miR-134 expression. H₂O₂-induced PC12 cell damage was improved by DEX and miR-134 inhibitor; additionally, cell viability was increased, while cell Apoptosis was reduced. In addition, both DEX and miR-134 inhibitor reduced the upregulated expression of cleaved Caspase-3 and increased the downregulated expression of Bcl-2 in H₂O₂-induced PC12 cells. However, compared to that in the DEX + H₂O₂ group, cell viability in the mimic + DEX + H₂O₂ group was decreased, and the apoptotic rate was elevated with increased cleaved Caspase-3 and decreased Bcl-2 expression. Inflammation and oxidative stress were increased in H₂O₂-induced PC12 cells but improved with DEX or miR-134 inhibitor treatment. However, this improvement of H₂O₂-induced inflammation and oxidative stress induced by DEX in PC12 cells could be reversed by the miR-134 mimic.

Conclusion: DEX exerts protective effects to promote viability and reduce cell Apoptosis, inflammation, and oxidative stress in H₂O₂-induced PC12 cells by inhibiting the expression of miR-134.