南京医科大学学报（自然科学版）2026，Vol.46Issue(9)：1303-1314,12.DOI:10.7655/NYDXBNSN260218
ReN细胞来源纳米囊泡中的let-7i-5p在帕金森病模型中通过抗凋亡作用发挥保护效应
The let-7i-5p in ReN cell-derived nanovesicles exerts neuroprotective effects via anti-apoptotic mechanisms in Parkinson's disease models
摘要
Abstract
Objective:To investigate the neuroprotective effects of nanovesicles(NVs)derived from the human neural stem cell line ReN cell and to explore the underlying molecular mechanisms in Parkinson's disease(PD).Methods:PD mouse models were established in C57BL/6 mice by intraperitoneal injection of 20 mg/kg 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP).Mice were treated via tail vein injection with nanovesicles obtained from extruded ReN cells(ReN-NV)or RVG peptide-modified ReN-NV(RVG-ReN-NV).Motor function was evaluated by the rotarod test and the pole test,and immunofluorescence staining was performed to assess the expression of tyrosine hydroxylase(TH)and the microglial marker Iba1 in the substantia nigra,as well as TH expression in the striatum.Western blot analysis was used to determine TH protein levels in the striatum.In vitro,a PD cell model was established by treating human neuroblastoma SH-SY5Y cells with 1 mmol/L 1-methyl-4-phenylpyridinium ion(MPP+).Cell viability was assessed using the CCK-8 assay,cytotoxicity was evaluated by lactate dehydrogenase(LDH)release assay,and the protein expression levels of Bcl-2 and Bax were measured by Western blotting.Results:The behavioral results showed that MPTP-treated mice displayed a significantly reduced latency to fall during the pole test,accompanied by an increased total descent time,suggesting the establishment of Parkinsonian-like motor impairment.Immunofluorescence analysis showed that ReN-NV alleviated the loss of TH-positive neurons in the substantia nigra and striatum induced by MPTP and reduced Iba1 expression in the substantia nigra,with RVG-ReN-NV exhibiting a more pronounced protective effect.Western blot analysis demonstrated that ReN-NV upregulated TH protein expression in the striatum.In vitro experiments showed that ReN-NV increased the viability of MPP+-treated SH-SY5Y cells,reduced LDH release,upregulated the expression of the anti-apoptotic protein Bcl-2,and downregulated the expression of the pro-apoptotic protein Bax.Conclusion:ReN cell-derived nanovesicles exert significant neuroprotective effects in MPTP/MPP+-induced PD models.RVG modification further enhances their brain-targeting protective efficacy,and the underlying mechanism may be associated with let-7i-5p-mediated inhibition of apoptotic pathways.关键词
外泌体/帕金森病/纳米囊泡/狂犬病毒糖蛋白肽Key words
exosomes/Parkinson's disease/nanovesicles/rabies virus glycoprotein peptide分类
医药卫生引用本文复制引用
魏甲园,徐聖业,朱妍妍,齐翠,尤卫艳,高隽..ReN细胞来源纳米囊泡中的let-7i-5p在帕金森病模型中通过抗凋亡作用发挥保护效应[J].南京医科大学学报（自然科学版）,2026,46(9):1303-1314,12.基金项目
国家自然科学基金(32371053,81973308) （32371053,81973308）
江苏省高校自然科学基金(18KJB180017) （18KJB180017）
