Abstract
Background Ferroptosis is emerging as a critical pathway in ischemia/reperfusion (I/R) injury,
contributing to compromised cardiac function and predisposing individuals to sepsis
and myocardial failure. The study investigates the underlying mechanism of dexmedetomidine
(DEX) in hypoxia/reoxygenation (H/R)-induced ferroptosis in cardiomyocytes, aiming
to identify novel targets for myocardial I/R injury treatment.
Methods H9C2 cells were subjected to H/R and treated with varying concentrations of DEX.
Additionally, H9C2 cells were transfected with miR-141-3p inhibitor followed by H/R
treatment. Levels of miR-141-3p, long noncoding RNA (lncRNA) taurine upregulated 1
(TUG1), Fe2+, glutathione (GSH), and malondialdehyde were assessed. Reactive oxygen species (ROS)
generation was measured via fluorescent labeling. Expression of ferroptosis-related
proteins glutathione peroxidase 4 (GPX4) and acyl-CoA synthetase long-chain family
member 4 (ACSL4) was determined using Western blot. The interaction between miR-141-3p
and lncRNA TUG1 was evaluated through RNA pull-down assay and dual-luciferase reporter
gene assays. The stability of lncRNA TUG1 was assessed using actinomycin D.
Results DEX ameliorated H/R-induced cardiomyocyte injury and elevated miR-141-3p expression
in cardiomyocytes. DEX treatment increased cell viability, Fe2+, and ROS levels while decreasing ACSL4 protein expression. Furthermore, DEX upregulated
GSH and GPX4 protein levels. miR-141-3p targeted lncRNA TUG1, reducing its stability
and overall expression. Inhibition of miR-141-3p or overexpression of lncRNA TUG1
partially reversed the inhibitory effect of DEX on H/R-induced ferroptosis in cardiomyocytes.
Conclusion DEX mitigated H/R-induced ferroptosis in cardiomyocytes by upregulating miR-141-3p
expression and downregulating lncRNA TUG1 expression, unveiling a potential therapeutic
strategy for myocardial I/R injury.
Keywords
dexmedetomidine - ischemia/reperfusion - myocardial - ferroptosis - miR-141-3p
