基础医学与临床2026，Vol.46Issue(7)：957-964,8.DOI:10.16352/j.issn.1001-6325.2026.07.0957
小鼠胰腺癌细胞系Pan02来源外泌体有效改善帕金森病模型小鼠运动功能障碍
Murine pancreatic cancer cell line Pan02-derived exosomes effectively improve motor dysfunction in mouse models of Parkinson's disease
摘要
Abstract
Objective To investigate the therapeutic effects of murine pancreatic cancer cell line Pan02l-derived exosomes(Exos)on Parkinson's disease(PD)in a mouse model.Methods Pan02 cell-derived exosomes were ex-tracted by commercially available kit and then characterized by transmission electron microscape(TEM),nanoparti-cle tracking analysis and Western blot.In vitro,the protective effect of exosomes on a mouse model of 1-methyl-4-phenylpyridinium(MPP+)-induced MN9D dopaminergic neuron injury was detected by CCK-8 assay.A C57BL/6J mice of acute 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)-induced PD was established.The mice were divided into a wild-type(WT)control group,a PD model group,and low,medium,and high-dose exosome groups(Exo-L,Exo-M,Exo-H).Exosomes were administered via multiple tail vein injections.Motor function and neurobehavioral changes were assessed using the balance beam test,pole test,rotarod test,open field test and Y-maze test.Damage to dopaminergic neurons in the substantia nigra and striatum was evaluated by immunofluores-cence microscopy.A tumor-bearing mouse model was also established for a preliminary safety evaluation.Results Exosomes markedly reversed the MPP+-induced decrease in MN9D cell viability(P＜0.001).Compared with the PD model group,the Exo-L group showed a substantial reduction in beam crossing time(P＜0.001)and pole de-scent time(P＜0.05).The Exo-M group exhibited a significant decrease in total distance moved in the open field test(P＜0.05).No notable differences were observed in anxiety and cognition-related behavioral parameters among all groups.Exosomes dramatically mitigated MPTP-induced loss of tyrosine hydroxylase(TH)-positive neurons in the substantia nigra(Exo-L group,P＜0.05;Exo-H group,P＜0.01)and reduction of TH-positive fiber density in the striatum(Exo-L and Exo-M groups,P＜0.05).Safety evaluation confirmed that exosomes did not promote tumor growth in tumor-bearing mice.Conclusions Pan02 cell-derived exosomes effectively alleviate MPP+/MPTP-induced dopaminergic neuron injury,ameliorate motor dysfunction in PD mouse models,and exhibit no tumor-pro-moting risk,demonstrating favorable neuro-protective effects and safety.关键词
帕金森病/1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)/Pan02细胞/外泌体Key words
Parkinson's disease/1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine(MPTP)/Pan02 cell/exosome分类
医药卫生引用本文复制引用
张可昕,肖芳艳,李文华,黄薇,刘雁勇,杨楠..小鼠胰腺癌细胞系Pan02来源外泌体有效改善帕金森病模型小鼠运动功能障碍[J].基础医学与临床,2026,46(7):957-964,8.基金项目
中国医学科学院医学与健康科技创新工程(2021-I2M-1-020) （2021-I2M-1-020）
