Dexmedetomidine improves propofol-induced neuronal injury in rat hippocampus with the involvement of miR-34a and the PI3K/Akt signaling pathway.

Aims: Dexmedetomidine (DEX) is a selective agonist of α-adrenergic receptors with anesthetic attributes and neuroprotective effects. This study was designed to explore the mechanisms of DEX in the propofol-induced neuronal injury in rat hippocampus.

Materials And Methods: Rat hippocampi were treated with propofol, and then neuronal injury, neuronal apoptosis, PSD and apoptosis-related protein expression in CA1 region were measured after DEX administration and/or ant-miR-34a. miR-34a expression was detected using RT-qPCR, while the binding of miR-34a and Sirtuin1 (SIRT1) was identified with dual luciferase reporter gene assay, and the activation of PI3K/Akt signaling pathway was detected. Additionally, hippocampal neurons were cultured in vitro and treated with DEX and propofol. The viability and apoptosis of hippocampal neurons, fluorescence intensity of Ca and neuronal morphology were detected.

Key Findings: In vivo experiments, propofol induced obvious neuronal injury in rat hippocampus, while DEX at different doses reduced hippocampal neuronal apoptosis and miR-34a expression but increased PSD expression in rat hippocampus. Low expression of miR-34a reduced propofol-induced neuronal injury by targeting SIRT1 and activating the PI3K/Akt pathway. In vitro experiments, propofol induced neuronal injury, which was alleviated by DEX treatment, accompanied with increased neuronal viability, but decreased apoptosis and fluorescence intensity of Ca. The attenuation of neuronal injury achieved by DEX was impaired by over-expression of miR-34a. Meanwhile, over-expression of SIRT1 in neurons with overexpressed miR-34a improved p-Akt and p-PI3K expression.

Significance: DEX could inhibit propofol-induced neuronal injury in rat hippocampus by inhibiting miR-34a expression, upregulating SIRT1 and activating the PI3K/Akt pathway.