Sevoflurane pre-treatment attenuates myocardial cell ferroptosis caused by hypoxia and reoxygenation via regulating lncRNA NNT-AS1.

Myocardial ischemia-reperfusion injury (MIRI) is the primary cause of death for acute myocardial infarction. LncRNA NNT-AS1 was upregulated in the H9c2 hypoxia-reoxygenation (H/R) model. However, the interaction between sevoflurane and NNT-AS1 is unknown in MIRI. The specific aim of this study was to explore the mechanism by which sevoflurane regulates cardiomyocyte injury via the NNT-AS1/miR-23a-3p/USP24 axis. The Caspase-3 level and apoptosis rate were used to assess the cell apoptosis level. Reactive oxygen species (ROS), malondialdehyde (MDA), glutathione (GSH), glutathione disulfide (GSSG), GSH/GSSG ratio, the total iron content, and Glutathione Peroxidase 4 (GPX4) protein content were measured to evaluate the level of ferroptosis. The targeting relationship was detected by the dual-luciferase reporter gene assay. In the H9c2 H/R model, the NNT-AS1 and USP24 levels were increased, but miR-23a-3p was decreased. The cell damage was aggravated, and apoptosis and ferroptosis were promoted. However, the NNT-AS1 and USP24 expression was downregulated, and miR-23a-3p expression was upregulated by sevoflurane pre-treatment. Cell damage, apoptosis, and ferroptosis were also improved. NNT-AS1 functions as a molecular sponge for miR-23a-3p. The NNT-AS1 overexpression further aggravated cell damage, apoptosis, and ferroptosis, while miR-23a-3p overexpression reversed the damaging effect of NNT-AS1. In summary, sevoflurane pretreatment alleviates apoptosis and ferroptosis in H/R-stimulated cardiomyocytes by regulating the NNT-AS1/miR-23a-3p/USP24 signaling axis, which may provide a potential target for MIRI treatment.