MiR-۱۲۴ alleviates cerebral ischemia-reperfusion injury by targeting SLC۱A۵ to inhibit neuronal ferroptosis

Objective(s): This study aimed to investigate whether miR-۱۲۴ alleviates neurological injury in cerebral ischemia-reperfusion injury (CIRI) mice by targeting Solute Carrier Family ۱ Member ۵ (SLC۱A۵) to regulate ferroptosis. Materials and Methods: One hundred twenty male C۵۷BL/۶ mice were randomly assigned to Sham, CIRI model, miR-۱۲۴ mimic, miR-۱۲۴ inhibitor, miR-۱۲۴ vector, and Ferrostatin-۱ (Fer-۱) groups. One week before modeling, the viral groups received ۲.۰ μl of the corresponding viral vector via right lateral ventricle injection. Additionally, the Fer-۱ group received intraperitoneal injections of ferrostatin-۱ (۵.۰ mg/kg). Following the establishment of the MCAO model by the wire occlusion method. At different time points, the Longa method was employed to assess the degree of neurological deficit. TTC staining was used to detect cerebral infarction volume. ELISA was applied to measure changes in SOD, MDA, GSH, and Fe²⁺. qRT-PCR was utilized to detect the expression levels of miR-۱۲۴, SLC۱A۵, and GPX۴, and Immunohistochemistry was detected SLC۱A۵-positive cells. Finally, the miR-۱۲۴/SLC۱A۵ interaction was predicted by bioinformatics and validated by a dual-luciferase assay and western blot.Results: Compared with the sham group, the CIRI group showed reduced neurological scores, elevated MDA/Fe²⁺, and decreased SOD/GSH/GPX۴. miR-۱۲۴ mimic treatment significantly improved these parameters, similar to Fer-۱, whereas miR-۱۲۴ inhibition exacerbated injury and increased SLC۱A۵ expression. Dual-luciferase assay confirmed SLC۱A۵ as a direct target of miR-۱۲۴.Conclusion: Collectively, these data indicate that MiR-۱۲۴ attenuates CIRI-induced neurological damage, potentially by targeting SLC۱A۵ to inhibit ferroptosis, as evidenced by up-regulation of GPX۴ and GSH.

کلیدواژه ها:

Cerebral ischemia ، Ferroptosis ، MiR-۱۲۴ ، Neuroprotection ، Reperfusion injury ، Solute carrier family ۱ member ۵