山西医科大学学报2025，Vol.56Issue(11)：1260-1267,8.DOI:10.13753/j.issn.1007-6611.2025.11.008
小胶质细胞来源外泌体改善脑卒中后认知行为的作用及其机制
Role and mechanism of microglia-derived exosomes in improving post-stroke cognitive behavior
摘要
Abstract
Objective To investigate the effects of microglia-derived exosomes(MDEs)on post-stroke cognitive function and eluci-date the underlying molecular mechanisms.Methods The rats were divided into three groups:sham group(sham operation),model group(MCAO),and MDEs group(MCAO+MDEs treatment).The rats in model group and MDEs group underwent middle cerebral artery occlusion surgery to establish the ischemic stroke model.After model establishment,the rats in MDEs group received MDEs treatment.The rats in sham group only underwent surgical incision and wound suturing.Microglial exosomes were isolated by ultra-centrifugation,and their structure(approximately 100 nm in diameter)was analyzed by transmission electron microscopy.Western blot was used to detect the expressions of exosomal markers CD9,CD63,and TSG101.Nanoparticle tracking analysis(NTA)was em-ployed to determine the particle size and the concentration of exosomes.The Morris water maze test was used to assess the effects of MDEs on escape latency,number of platform crossing,and time spent in the target quadrant.The novel object recognition test was applied to evaluate the recognition index.The mRNA expression levels of inflammatory factors(IL-1β,TNF-α)and neuroplasticity-related molecules(brain-derived neurotrophic factor and Synaptophysin)in hippocampal tissue were detected by qPCR.Immunofluo-rescence of NeuN staining was used to further analyze the effect of MDEs on neuronal synaptic growth length.Results The exosomal marker proteins CD9,CD63,and TSG101 were highly expressed in MDEs,and the size distribution and concentration characteristics met the standard criteria for exosomes.In the Morris water maze test,the spatial learning ability in model group was significantly decreased compared with sham group(P<0.05),while the spatial learning ability was improved in MDEs group compared with model group(P<0.05),as evidenced by a significant shortening of escape latency over the training period,eventually reaching a level compa-rable to that of sham group.In the spatial memory test of water maze,both the number of platform crossing and the time spent in the target quadrant significantly increased in MDEs group compared with model group(P<0.05),and the parameters were close to the levels in sham group.The novel object recognition test results indicated that compared with model group,the recognition memory ability of rats was significantly enhanced in MDEs group(P<0.05),and their cognitive function recovered to the level in sham group.Compared with model group,the inflammatory response was significantly reduced in MDEs group,manifested by the down-regulated expressions of IL-1β and TNF-α(P<0.05),and the up-regulated expressions of BDNF and Synaptophysin(P<0.05).Immunofluorescence result confirmed that compared with model group,the abilities of synaptic remodeling and regeneration after injury were significantly enhanced in MDEs group(P<0.05).Conclusion MDEs-derived exosomes can improve spatial learning,memory,and recognition cognitive functions in ischemic stroke rats through exerting anti-inflammatory effects and promoting neural plasticity.关键词
小胶质细胞外泌体/神经炎症/神经再生/认知功能障碍/突触素/脑源性神经营养因子/缺血性脑卒中Key words
microglia-derived exosomes/neuroinflammation/neuroregeneration/cognitive dysfunction/synaptophysin/brain-derived neurotrophic factor/ischemic stroke分类
医药卫生引用本文复制引用
CHEN Hao,WANG Yaoting,SHI Bohan,LI Wei,ZHU Yan..小胶质细胞来源外泌体改善脑卒中后认知行为的作用及其机制[J].山西医科大学学报,2025,56(11):1260-1267,8.基金项目
上海市宝山区卫健委英才计划项目(BSWSYX-2024-03) （BSWSYX-2024-03）
宝山区卫健委重点专科项目(BSZK-2023-A17) （BSZK-2023-A17）
