中山大学学报（医学科学版）2026，Vol.47Issue(4)：681-689,9.DOI:10.11714/jsysu.med.YX20260055
RAGE-STAT3通路介导帕金森模型纹状体神经元线粒体损伤
Mechanism of RAGE-STAT3 Pathway-mediated Mitochondrial Injury in Striatum Neurons of Parkinson's Disease Model
摘要
Abstract
[Objective]To investigate the molecular mechanisms by which the receptor for advanced glycation end products(RAGE)-signal transducer and activator of transcription 3(STAT3)signaling pathway mediates mitochondrial injury in striosome/matrix compartment neurons under dopaminergic depletion in Parkinson's disease(PD).[Methods]A 6-hydroxydopamine(6-OHDA)-induced rat model of PD was established and treated with the RAGE inhibitor FPS-ZM1.Immunohistochemistry,double immunofluorescence staining,transmission electron microscopy(TEM),Western blotting,and quantitative real-time PCR(qRT-PCR)were performed to evaluate RAGE and STAT3 expression as well as mitochondrial ultrastructure alterations in the striosome/matrix compartment.[Results]The density of RAGE-positive structures and the protein expression level of RAGE in the striosome/matrix compartment were significantly increased in PD rats compared with controls(P<0.05).Immunohistochemical and double immunofluorescence analyses demonstrated widespread STAT3 expression in striatal neurons,while the number of NeuN/STAT3 double-positive cells was significantly elevated in the PD group(P<0.05).Western blotting and qRT-PCR further confirmed significant upregulation of STAT3 protein and mRNA expression in PD rats(P<0.05).TEM analysis revealed marked mitochondrial abnormalities in PD neurons,including reduced mitochondrial density,enlarged mitochondrial area,decreased cristae number,cristae membrane disruption,and outer membrane damage(all P<0.05).Notably,FPS-ZM1 treatment partially reversed these mitochondrial ultrastructural alterations.[Conclusion]Activation of the RAGE-STAT3 signaling pathway contributes to mitochondrial structural disruption in striosome/matrix compartment neurons in PD.These findings suggest that the striosome/matrix compartment may represent a novel pathological target for investigating mitochondrial dysfunction and neurodegeneration in PD.关键词
帕金森病/晚期糖基化终末产物受体/信号转导与转录激活因子3/纹状小体/线粒体/多巴胺Key words
Parkinson's disease/receptor for advanced glycation end products/signal transducer and activator of transcription 3/striosomes/mitochondria/dopamine分类
医药卫生引用本文复制引用
郭威,田滕梓,朱耀峰..RAGE-STAT3通路介导帕金森模型纹状体神经元线粒体损伤[J].中山大学学报（医学科学版）,2026,47(4):681-689,9.基金项目
国家自然科学基金(82260264) （82260264）
湖南省自然科学基金(2025JJ50707) （2025JJ50707）
湖南省教育厅重点项目(23A0397) （23A0397）
