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基于DIA定量蛋白质组学解析电针对阿尔茨海默病模型大鼠认知功能的改善机制

Analysis of the Improvement Mechanism of Electroacupuncture on Cognitive Function in Alzheimer’s Disease Model Rats Based on DIA Quantitative Proteomics
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摘要 目的采用数据非依赖采集(DIA)定量技术对接受电针干预的阿尔茨海默病(AD)模型大鼠海马组织进行蛋白质组学分析,探究电针改善AD模型大鼠认知功能的作用机制。方法本研究于2023年10月至2023年11月在深圳市众循精准医学研究院进行,将15只AD模型大鼠用随机数字表法分为电针治疗组(ZD组)、假针刺组(ZW组)及模型组(M组),每组5只。ZD组于双侧“天枢”“曲池”及“足三里”穴位行电针治疗;ZW组于上述穴位旁开5 mm非经穴处实施假电针干预;M组仅接受与ZD组等时长的束缚固定,不施加任何针刺或电刺激。各组每日干预1次,每次30 min,连续14 d,干预结束后进行新物体识别测试(NORT)和DIA定量蛋白质组学分析。结果NORT显示,ZD组辨别指数(DI)高于ZW组和M组,差异有统计学意义(P<0.05),其总探索时间长于ZW组和M组,差异有统计学意义(P<0.05)。DIA定量蛋白质组学分析表明,相较于M组,ZD组海马组织中鉴定出16个差异上调表达蛋白及13个差异下调表达蛋白。差异表达蛋白主要定位于细胞质膜,GO富集分析显示其在突触及突触后结构富集,KEGG富集分析揭示其在谷氨酸能突触富集,Reactome富集分析则表明其富集在信号转导通路。结论电针可有效改善AD模型大鼠的认知功能障碍,其作用机制可能通过调控谷氨酸能突触相关的差异表达蛋白,进而改善突触功能,促进兴奋性神经信号传导。 Objective To conduct proteomic analysis of hippocampal tissue in Alzheimer’s disease(AD)model rats receiving electroacupuncture intervention using Data Independent Acquisition(DIA)quantitative technology,and explore the mechanism of electroacupuncture improving cognitive function in AD model rats.Methods From October 2023 to November 2023,fifteen AD model rats were randomly divided into electroacupuncture treatment group(ZD group),sham acupuncture group(ZW group)and model group(M group),with five rats in each group.The ZD group received electroacupuncture treatment at the“Tian Shu”,“Qu Chi”and“Zu San Li”acupoints on both sides.The ZW group performed sham electroacupuncture intervention at 5 mm non-meridian acupoints adjacent to the above-mentioned acupoints.The M group only received restraint fixation of the same duration as the ZD group,without any acupuncture or electrical stimulation.Each group was intervened once a day for 30 minutes each time for 14 consecutive days.After the intervention,Novel Object Recognition Test(NORT)and DIA quantitative proteomics analysis were performed.Results NORT showed that the Discrimination Index(DI)of the ZD group was higher than that of the ZW group and the M group(P<0.05),and the total exploration time was longer than that of the ZW group and the M group(P<0.05).DIA quantitative proteomics analysis showed that compared to the M group,16 differentially upregulated proteins and 13 differentially downregulated proteins were identified in the hippocampal tissue of the ZD group.Differentially expressed proteins were mainly localized on the Plasma membrane.GO enrichment analysis showed their enrichment in synapse and postsynapse,KEGG enrichment analysis revealed their enrichment in Glutamatergic synapse,and Reactome enrichment analysis showed their enrichment in Signal Transduction pathways.Conclusions Electroacupuncture can effectively improve cognitive dysfunction in AD model rats,and its mechanism of action may be through regulating differentially expressed proteins related to Glutamatergic synapse,thereby improving synaptic function and promoting excitatory nerve signal transduction.
作者 毕钰桢 罗粤铭 赵海梅 程晶 郭红 胡毅澜 程红 BI Yuzhen;LUO Yueming;ZHAO Haimei;CHENG Jing;GUO Hong;HU Yilan;CHENG Hong(Department of Geriatric,Shenzhen Traditional Chinese Medicine Hospital,Shenzhen,Guangdong 518000,China)
出处 《中国医药指南》 2025年第33期60-64,共5页 Guide of China Medicine
基金 深圳市科技计划项目(JCYJ20220531092014033) 深圳市“医疗卫生三名工程”项目资助(SZZYSM202411009) 深圳市卫生健康委“十四五”鹏城岐黄工程深圳市中医药优秀人才培养项目。
关键词 阿尔茨海默病 电针 大鼠 认知功能 数据非依赖采集 蛋白质组学 Alzheimer’s disease Electroacupuncture Rats Cognitive function Data independent acquisition Proteomics
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