Dexmedetomidine regulates sevoflurane-induced neurotoxicity through the miR-330-3p/ULK1 axis

Sevoflurane (Sev), a widely used volatile anesthetic, can cause long-term neurotoxicity and learning and memory impairment. Dexmedetomidine (Dex) has been reported to exhibit neuroprotective effects in numerous neurological disorders. Our work aimed to evaluate the molecular mechanisms of Dex in Sev-induced neurotoxicity. In this study, it was found that Dex mitigated Sev-induced neurotoxicity. Moreover, Sev treatment upregulated the miR-330-3p expression in hippocampus tissues, while this effect was reversed by the Dex treatment. Additionally, microRNA-330-3p (miR-330-3p) inhibition was verified to inhibit cell apoptosis and facilitate mitophagy. ULK1 was confirmed as a downstream target of miR-330-3p and miR-330-3p could negatively regulate ULK1 expression. Finally, the effects of miR-330-3p inhibition on Sev-induced neurotoxicity could be offset by ULK1 knockdown or further intensified by Dex treatment. In summary, our study demonstrated that Dex regulated cell apoptosis and mitophagy in Sev-induced neurotoxicity through the miR-330-3p/ULK1 axis. These findings might provide novel insights into the treatment of Sev-induced neurotoxicity.