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RBM15B在阿尔茨海默病中的表达变化及其对神经元损伤的影响OA

Expression of RBM15B in Alzheimer's disease and its effect on neuronal damage

中文摘要英文摘要

目的 探讨RNA结合基元蛋白15B(RBM15B)在阿尔茨海默病(AD)中的表达变化及其对神经元损伤的影响.方法 通过AlzData数据库分析RBM15B在AD患者不同脑区的表达.建立Aβ25-35诱导的PC-12细胞AD模型,检测不同浓度Aβ25-35 对RBM15B表达的影响.通过siRNA敲低和过表达载体转染调控RBM15B的表达水平,观察其对细胞活力和凋亡的影响.建立APP/PS1转基因AD小鼠模型,进行行为学检测和Western blot分析.结果 生信分析显示,RBM15B在AD患者额叶皮层和内嗅皮层显著上调表达.随着Aβ25-35 浓度增加,PC-12细胞中RBM15B表达呈浓度依赖性增加,同时细胞活力下降、凋亡增加.RBM15B敲低能够显著改善Aβ25-35诱导的细胞损伤,过表达则显著加重细胞损伤.AD小鼠大脑组织中 RBM15B 蛋白表达显著升高,同时表现出显著的学习记忆障碍和新物体识别能力下降.结论 RBM15B在AD患者和AD模型中均显著上调表达,其高表达可加重神经元损伤,敲低RBM15B表达对神经元具有保护作用,提示RBM15B可能是AD治疗的潜在靶点.

Objective To investigate the expression of RNA binding motif protein 15B(RBM15B)in Alzheimer's disease(AD)and its effect on neuronal injury.Methods The expression of RBM15 B in different brain regions of AD patients was analyzed by AlzData database.The AD model of PC-12 cells induced by Aβ25-35 was established to detect the effect of different concentrations of Aβ 25-35 on the expression of RBM15B.The expression level of RBM15B was regulated by siRNA knockdown and overexpression vector transfection,and the effects on cell viability and apoptosis were observed.APP/PS1 transgenic AD mouse model was established for behavioral detection and Western blot analysis.Results Bioinformatics analysis showed that RBM15B was significantly up-regulated in the frontal cortex and entorhinal cortex of AD patients.With the increase of A β 25-35 concentration,the expression of RBM15B in PC-12 cells increased in a concentration-dependent manner,while the cell viability decreased and the apoptosis increased.RBM15B knockdown significantly improved Aβ25-35-induced cell damage,while overexpression significantly aggravated cell damage.The expression of RBM15B protein in the brain tissue of AD mice was significantly increased,and showed significant learning and memory impairment and decreased new object recognition ability.Conclusion RBM15B is significantly up-regulated in AD patients and AD models,and its high expression can aggravate neuronal damage.Knockdown of RBM15B expression has a protective effect on neurons,suggesting that RBM15B may be a potential target for AD treatment.

陈庆;金伟峰;陈姝子;李丹;徐青青;林萍

上海市精神卫生中心,上海 200030上海市精神卫生中心,上海 200030上海市精神卫生中心,上海 200030上海市精神卫生中心,上海 200030上海市精神卫生中心遗传生化实验室,上海 200030上海市精神卫生中心,上海 200030

医药卫生

阿尔茨海默病RNA结合基元蛋白15B神经元损伤细胞凋亡认知功能

Alzheimer's diseaseRBM15BNeuronal damageCell apoptosisCognitive function

《中国实用神经疾病杂志》 2026 (2)

133-139,7

上海市卫生健康委员会医学新技术研究与转化种子计划项目(编号:2024ZZ1032)

10.12083/SYSJ.251503

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