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 (HO)-stimulated PC12 cells were divided into control, HO, DEX + HO, miR-NC/inhibitor + HO, and miR-NC/ mimic + DEX + HO 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 HO-elevated miR-134 expression. HO-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 HO-induced PC12 cells. However, compared to that in the DEX + HO group, cell viability in the mimic + DEX + HO 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 HO-induced PC12 cells but improved with DEX or miR-134 inhibitor treatment. However, this improvement of HO-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 HO-induced PC12 cells by inhibiting the expression of miR-134.