南方医科大学学报2026，Vol.46Issue(5)：1018-1027,10.DOI:10.12122/j.issn.1673-4254.2026.05.05
miR-143-3p通过靶向KRAS/RalA通路抑制星形胶质细胞活化并缓解坐骨神经分支选择性损伤小鼠神经病理性疼痛
miR-143-3p alleviates neuropathic pain in mice with spared nerve injury by targeting the KRAS/RalA pathway and inhibiting astrocyte activation
摘要
Abstract
Objective To investigate the therapeutic effect of microRNA(miR-143-3p)on neuropathic pain in mice and clarify its target gene and molecular mechanism.Methods Spared nerve injury(SNI)models were established in 8-week-old male C57BL/6J mice,with sham-operated mice as the control group(n=6).The treatment group received a single intrathecal injection of miR-143-3p agomir on day 7 after SNI modeling,and in KRAS agonist group,KRA-533 was intrathecally injected on day 8 following miR-143-3p agomir injection.Mechanical withdrawal thresholds of the ipsilateral paw of the mice were measured using von Frey filaments.Bioinformatics analyses were used to explore the potential targets and signaling pathways.In a C8-D1A astrocyte model of lipopolysaccharide(LPS)-induced inflammation,the effect of miR-143-3p mimic and KRA-533 on the expressions of the identified targets were detected using qRT-PCR and Western blotting.Spinal morphology in the mouse models and proliferative activity of C8-D1A cells were observed with immunofluorescence staining,and the levels of pro-inflammatory factors were determined with enzyme-linked immunosorbent assay(ELISA).Results miR-143-3p agomir significantly increased mechanical withdrawal thresholds of SNI mice,and the effect lasted nearly 3 weeks.KRAS was identified as a direct target of miR-143-3p.In SNI mouse models,miR-143-3p significantly inhibited KRAS expression,RalA/TBK1/NF-κB signaling pathway activation,and astrocyte activation,and upregulated the levels of IL-6,IL-1β,and TNF-α.The KRAS agonist KRA-533 significantly reversed the analgesic effect of miR-143-3p and its inhibitory effects on downstream pathway activation,astrocyte activation,and neuroinflammation.In C8-D1A cells,overexpression of miR-143-3p effectively suppressed LPS-induced noncanonical Ras pathway activation and inhibited cell proliferation and inflammatory response,which were reversed by treatment with KRA-533.Conclusion miR-143-3p overexpression alleviates neuropathic pain in mice by targeting KRAS to regulate the noncanonical Ras pathway and inhibiting astrocyte activation and neuroinflammation,suggesting a new strategy for clinical treatment of SNI.关键词
神经病理性疼痛/miR-143-3p/KRAS/星形胶质细胞/神经炎症Key words
neuropathic pain/miR-143-3p/KRAS/astrocytes/neuroinflammation引用本文复制引用
林奕歆,姚锦忠,陈晔明,秦再生..miR-143-3p通过靶向KRAS/RalA通路抑制星形胶质细胞活化并缓解坐骨神经分支选择性损伤小鼠神经病理性疼痛[J].南方医科大学学报,2026,46(5):1018-1027,10.基金项目
国家自然科学基金(81973305)Supported by National Natural Science Foundation of China(81973305). （81973305）
