Dexmedetomidine Protects Cortical Neurons from Propofol-Induced Apoptosis via Activation of Akt-IKK-NF-κB Signaling Pathway by α2A-adrenoceptor.

Abstract

Propofol can induce neuroapoptosis. It has been reported that dexmedetomidine (DEX) has a protective effect on propofol-induced neuroapoptosis, but the specific mechanism needs to be further explored to provide a theoretical basis for their combined use. We aimed to explore the neuroprotective effect of DEX on primary cortical neurons treated by propofol and to elucidate the underlying mechanistic pathways. Cortical neurons were isolated from fetal rats and treated with propofol. MTT assays were performed to detect cell viability, α-tubulin immunofluorescent assays were conducted to observe cell abnormalities, and c-caspase3 immunofluorescent assays and flow cytometry were performed to examine cell apoptosis. Further, neurons were cotreated with propofol and DEX to study DEX's neuroprotective effects on propofol-caused neuronal injuries. Finally, the α2A-adrenoceptor was knocked out and/or the Akt activator (SC-79) was added to cells co-treated with propofol and DEX. The expression levels of Akt-IKK-NF-κB pathway-related proteins were detected by western blot. Propofol decreased cell viability in a dose-dependent manner, triggered apoptosis, caused morphological abnormalities and down-regulated the phosphorylation levels of Akt, IKK, NF-κB and IκB in cortical neurons. DEX ameliorated the decrease of cell viability, alleviated neuronal apoptosis and promoted the downregulated expression levels of p-Akt, IKK, NF-κB, and IκB proteins which had been induced by propofol treatment. Western blot findings following the transfection of α2A-siRNA and the addition of SC-79 suggested that DEX's neuroprotective functions arose from the stimulation of α2A-adrenoceptors to activate the Akt-IKK-NF-κB signal pathway. DEX protected neurons against propofol-induced apoptosis via activation of the Akt-IKK-NF-κB signal pathway through α2A-adrenoceptors.