Mechanism of miR-140-3p reducing anesthesia induced neurotoxicity by downregulating BACE1 expression.

Abstract

Propofol is a widely employed intravenous general anesthetic that can induce neurotoxic effects on neurons. Previous research has indicated dysregulation of miR-140-3p in the hippocampal tissues of propofol-treated mice. This research was designed to investigate the function and underlying mechanism of miR-140-3p in propofol-induced neurotoxicity. To simulate propofol-induced neurotoxicity, human SH-SY5Y cells and mice were treated with propofol. Commercial kits were used to measure LDH, MDA, SOD, GSH-Px, and BDNF levels. Cells were transfected with miR-140-3p mimics, inhibitor, or BACE1 overexpression plasmids. Gene expression was assessed by RT-qPCR, cell viability by CCK-8, and apoptosis by flow cytometry. Dual-luciferase and RIP assays confirmed that miR-140-3p targets BACE1. The results confirmed that as the concentration of propofol increased, miR-140-3p levels were progressively downregulated, while BACE1 was correspondingly upregulated. Upregulation of miR-140-3p rescued propofol-treated SH-SY5Y cells from cytotoxicity, as evidenced by enhanced viability, suppressed apoptosis, and ameliorated oxidative stress. Consistently, miR-140-3p overexpression also attenuated propofol-induced neurotoxicity in vivo. Furthermore, BACE1 was confirmed to be a direct target of miR-140-3p through experimental validation, and this post-transcriptional repression was shown to mediate the observed neuroprotection. miR-140-3p attenuates propofol-induced neurotoxicity via BACE1 in vitro and in vivo, providing new insights and a potential biomarker for managing propofol-associated neurotoxicity.