lncRNA H19 contributes to sevoflurane-induced neuronal death in SH-SY5Y cells via ACSL4-mediated ferroptosis pathway.

Sevoflurane induces neurotoxicity and cognitive impairment, with long noncoding RNAs (lncRNAs) playing key roles in nervous system diseases. This study explored lncRNA H19's function in sevoflurane-induced neurotoxicity. SH-SY5Y cell viability and apoptosis were assessed via CCK8 and TUNEL assays. Gene expression was measured by RT-qPCR, while reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), and iron levels were quantified. Subcellular fractionation determined H19 localization, and luciferase assays confirmed H19/miR-20a-5p and miR-20a-5p/Acyl-CoA synthetase long chain family member 4 (ACSL4) interactions. Western blot analyzed ACSL4, apoptosis-, and ferroptosis-related proteins. The results showed that sevoflurane reduced viability, promoted apoptosis and ferroptosis, and upregulated H19 and ACSL4. H19 knockdown mitigated neurotoxicity by restoring viability, GSH, solute carrier family 7 member 11 (SLC7A11), and glutathione peroxidase 4 (GPX4), while reducing apoptosis, MDA, ROS, and iron. Mechanistically, H19 sponged miR-20a-5p to elevate ACSL4. Rescue assays showed miR-20a-5p inhibition or ACSL4 overexpression reversed H19 silencing's protective effects. Thus, H19 depletion alleviates sevoflurane-induced neuronal damage via the miR-20a-5p/ACSL4 axis, suggesting a potential therapeutic target.