川北医学院学报2026，Vol.41Issue(5)：529-534,6.DOI:10.3969/j.issn.1005-3697.2026.05.003
慢病毒下调Nrf2通过GCLC介导神经突触损伤加重AD认知障碍
Lentivirus-downregulated Nrf2 aggravates synaptic damage and cognitive impairment in AD by downregulating GCLC
摘要
Abstract
Objective:To explore the intrinsic mechanism of Nrf2 improving cognitive dysfunction in Alzheimer's disease(AD)through antioxidant effects.Methods:APP/PS1 mice were used as AD model mice,and the Nrf2 downregulated mouse model was established by injecting lentivirus into the hippocampus.Morris water maze test was used to evaluate the learning and memory ability of mice,and real-time quantitative polymerase chain reaction(RT-PCR)was used to detect the levels of Nrf2 mRNA.Western blotting was used to detect the expression of Nrf2,GCLC,and Aβ protein.Immunohistochemistry was used to observe the expression of Aβ protein in hippocampal tissue.Immunofluorescence was used to observe the expression of MAP2 in hippocampal tissue.Transmission electron microscopy was used to observe the structure of neural synapses.Results:Compared with the control group mice,the levels of Nrf2,GCLC protein and MAP2 in AD model mice were decreased,Aβ protein deposition increased,synaptic damage and cognitive impairment were aggravated(P<0.05).Lentivirus-induced Nrf2 downregulation downregulated GCLC protein expression,decreased MAP2 levels,and aggravates Aβ protein deposition,synaptic damage and cognitive impairment(P<0.05).Conclusion:Lentivirus-downregulated Nrf2 aggravated the oxidative stress re-sponse by downregulating GCLC,aggravates Aβ protein deposition and synaptic damage,and further aggravated the cognitive dysfunction of AD.关键词
Nrf2/阿尔茨海默病/突触损伤/认知障碍/氧化应激Key words
Nrf2/Alzheimer's disease/Synaptic damage/Cognitive impairment/Oxidative stress分类
医药卫生引用本文复制引用
徐玉珠,罗伟刚,张桂松,刘翠翠,胡晓凯,贾亚南,王泽艺,任慧玲..慢病毒下调Nrf2通过GCLC介导神经突触损伤加重AD认知障碍[J].川北医学院学报,2026,41(5):529-534,6.基金项目
河北省政府资助临床医学优秀人才培养项目(ZF2024090) （ZF2024090）
河北省医学科学研究课题计划(20190607) （20190607）
