• Na Xing, Fei Xing, Yanna Li, Pingle Li, Jianwen Zhang, Dongmei Wang, Wei Zhang, and Jianjun Yang.
• Department of Anesthesiology, Pain and Perioperative Medicine, The First Affiliated Hospital of Zhengzhou University, Henan, Zhengzhou 450000, PR China.
• Life Sci. 2020 Apr 15; 247: 117359.

AimsDexmedetomidine (DEX) is a selective agonist of α2-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 MethodsRat hippocampi were treated with propofol, and then neuronal injury, neuronal apoptosis, PSD95 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 Ca2+ and neuronal morphology were detected.Key FindingsIn 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 PSD95 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 Ca2+. 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.SignificanceDEX could inhibit propofol-induced neuronal injury in rat hippocampus by inhibiting miR-34a expression, upregulating SIRT1 and activating the PI3K/Akt pathway.Copyright © 2020. Published by Elsevier Inc.

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