miR-423-3p alleviates sevoflurane-induced learning and memory dysfunction and nerve damage via negative regulation of GPX4.

Abstract

Background: Sevoflurane anesthesia, while widely used, is associated with several side effects including the potential for nerve damage. MicroRNAs are disrupted in patients with sevoflurane anesthesia, including miR-423-3p. However, the association between miR-423-3p and neurological damage remains to be elucidated.

Aim: To investigate the effect of miR-423-3p on the rats after sevoflurane anesthesia and related molecular mechanisms.

Methods: RT-qPCR was utilized to quantify the levels of miR-423-3p, GPX4 and oxidative stress indicators in rat hippocampus. Cognitive function was assessed through the Morris water maze and novel object recognition tests. ELISA was applied to detect the levels of inflammatory factors.

Results: In the Sev group, miR-423-3p expression was significantly elevated, while GPX4 expression was markedly reduced. Down-regulated miR-423-3p negatively regulated GPX4 to shorten escape latency while increasing crossing times of the platform, time spend in the target quadrant, relative occupancy of exploring new objects and time to explore new objects. Furthermore, down-regulated miR-423-3p reduced ROS and MDA levels and increased GSH levels in nerve-injured rats, which could be reversed by inhibited GPX4. miR-423-3p inhibition reduced the levels of NLRP3, Caspase-1, IL-8, and IL-1β, which could be rescued by inhibition of GPX4.

Conclusion: Down-regulation of miR-423-3p attenuated cognitive deficits in nerve-injured rats. Moreover, repressed miR-423-3p mitigated oxidative stress and inflammation by negatively regulating GPX4.