Conclusion
These results suggest that Dex preconditioning can prevent MIRI by attenuating ferroptosis via α2 adrenergic receptor activation and by modulating the Nrf2/SLC7A11/GPX4 pathway.
Methods
Male Sprague-Dawley rats were randomly assigned to five groups: sham (saline-treated), I/R (ischemia-exposed), Dex + I/R (Dex pre-treatment), Dex + Yoh + I/R (Dex and yohimbine pre-treatment), and Yoh + I/R (yohimbine pre-treatment). Cardiac function, myocardial infarction, and morphological changes were assessed. Transmission electron microscopy was used to analyze mitochondrial morphology. Ferroptosis-related indicators and lipid peroxidation were measured using western blotting and qRT-PCR.
Objective
Dexmedetomidine (Dex) is a potent agonist of the α2 adrenergic receptor that has been shown to possess sedative and hypnotic properties. Dex can protect against myocardial ischemia-reperfusion injury (MIRI) by inhibiting ferroptosis. However, these studies were based on Dex post-conditioning, and the role of α2 adrenergic receptors in this process is unclear. In this study, we investigated whether Dex preconditioning can prevent MIRI by attenuating ferroptosis and whether this effect depends on α2 adrenergic receptors in rats.
Results
Our findings indicated that Dex preconditioning improved cardiac function, reduced infarct size and apoptosis, and inhibited ferroptosis in the rat myocardium after MIRI. These effects were associated with the upregulation of Nrf2, SLC7A11, and GPX4 expression, as well as the downregulation of Ferritin, TFR1, ACSL4, COX2, IL-1β, IL-6, and TNF-α expression. Importantly, yohimbine, an α2 adrenergic receptor antagonist, abolished these protective effects.