南方医科大学学报2026，Vol.46Issue(4)：715-727,13.DOI:10.12122/j.issn.1673-4254.2026.04.01
miR-24-3p靶向GSK-3β抑制铁死亡促进大鼠脊髓损伤修复
miR-24-3p promotes spinal cord injury repair in rats by inhibiting ferroptosis via targeting GSK-3β
摘要
Abstract
Objective To investigate the molecular mechanism by which miR-24-3p promotes spinal cord injury(SCI)repair in rats.Methods The changes in spinal cord miR-24-3p expression was detected in a SD rat model of SCI with qRT-PCR.Using a stereotaxic apparatus,miR-24-3p agomir or a negative control reagent was microinjected at 3 mm rostral and caudal to the SCI epicenter of the rats.Motor function recovery of the SCI rats was evaluated with BBB scores,histopathological changes and Fe²⁺content in the SCI area were examined with HE staining and a commercial assay kit,and the changes in iron deposition in the SCI area was observed using Prussian blue staining with DAB.Western blotting and immunofluorescence staining were used to detect expressions of glycogen synthase kinase-3β(GSK-3β)and ferroptosis-related proteins xCT and GPX4 in the injured tissue.The targeted regulatory relationship between miR-24-3p and GSK-3β was verified using dual-luciferase reporter assay.In PC12 cells with erastin-induced ferroptosis,malondialdehyde(MDA)content was detected and the expression levels of GSK-3β,xCT and GPX4 proteins were determined by Western blotting and immunofluorescence staining.Results The expression of miR-24-3p and protein levels of xCT and GPX4 were significantly decreased in the SCI area of the rat models.Treatment with miR-24-3p agomir significantly improved hindlimb motor function of the SCI rats,alleviated spinal cord pathologies,reduced Fe² ⁺ content,iron deposition and GSK-3β protein expression,and upregulated xCT and GPX4 protein expressions in the SCI area.Dual-luciferase reporter assay confirmed targeted inhibition of GSK-3β by miR-24-3p.In erastin-induced PC12 cells,transfection with miR-24-3p mimics significantly decreased intracellular MDA content and GSK-3β protein expression and increased xCT and GPX4 protein levels,and these effects were enhanced by co-transfection with GSK-3β inhibitor.Conclusion miR-24-3p promotes repair of SCI in rats by inhibiting ferroptosis via targeted suppression of GSK-3β.关键词
脊髓损伤/miR-24-3p/GSK-3β/铁死亡Key words
spinal cord injury/miR-24-3p/glycogen synthase kinase-3β/ferroptosis引用本文复制引用
魏栋敏,陈晨,赵琳,王冰冰,高建忠,翟天宇,白心悦,朱晶惠,张灿,施彩珍,郝琴..miR-24-3p靶向GSK-3β抑制铁死亡促进大鼠脊髓损伤修复[J].南方医科大学学报,2026,46(4):715-727,13.基金项目
Supported by National Natural Science Foundation of China(81641048),Shaanxi Social Development of Science and Technology Project(2021SF-082,2025SF-YBXM-014),and Research Project of Yan'an University(2023JBZR-011). 基金项目:国家自然科学基金(81641048) （81641048）
陕西省科技厅项目(2021SF-082,2025SF-YBXM-014) （2021SF-082,2025SF-YBXM-014）
延安大学科技项目(2023JBZR-011) （2023JBZR-011）
