Work

Hydrogen sulfide modulates the miR-27a/SLC7A11 axis to inhibit ferroptosis and reduce neuronal damage in ischemic stroke

Year: 2025

Type: article

Abstract: Ischemic stroke (IS) is a major global cause of mortality and long-term disability, and effective therapies are urgently needed. Hydrogen sulfide (H 2 S) has shown neuroprotective effects in various neurological disorders, but its mechanisms in IS remain unclear. This study aims to explore the role and mechanism of H 2 S in IS treatment. IS models were established in vivo using middle-cerebral-artery occlusion (MCAO) in rats and in vitro using oxygen-glucose deprivation/reoxygenation (OGD/R) in PC12 cells. These models were treated with H 2 S donors NaHS or GYY4137. Pathological features were evaluated using TTC, FJC, H&E, and Nissl staining. Cell viability was assessed with live/dead staining and CCK-8 assay. RNA sequencing identified gene expression changes after H 2 S treatment under OGD/R conditions. Ferroptosis-related markers, lipid peroxidation (GSH, SOD, MDA), ROS levels, and the expression of SLC7A11 and GPX4 were measured by flow cytometry, Western blot, and immunofluorescence. MiR-27a levels were quantified by qRT-PCR. NaHS administration in MCAO rats reduced infarct volume, increased Nissl body density, and decreased degenerating neurons. GYY4137 exhibited similar neuroprotective effects in vitro. RNA sequencing revealed that GYY4137 reversed ferroptosis-related gene changes, including SLC7A11. H 2 S supplementation inhibited neuronal ferroptosis, shown by increased SLC7A11 and GPX4 expression, elevated GSH and SOD levels, and reduced MDA content. Additionally, MCAO or OGD/R induced miR-27a expression, which negatively regulated SLC7A11. H 2 S reversed this induction, and miR-27a overexpression partially blocked the anti-ferroptotic effect of H 2 S. H 2 S alleviated IS-induced brain injury by suppressing ferroptosis, partially through miR-27a-dependent regulation of SLC7A11. These findings suggest H 2 S as a promising therapeutic agent for IS, warranting further clinical exploration.

Source: Journal of Radiation Research and Applied Sciences

DOI: 10.1016/j.jrras.2025.102035