EFhd1/2在AD患者及模型小鼠中的表达对比研究  

A comparative study on the expression of EFhd1/2 in AD patients and model mice

作　　者：谢非 李晓恒 程金波 任振华 袁增强 Xie Fei;Li Xiaoheng;Cheng Jinbo;Ren Zhenhua;Yuan Zengqiang(Dept of Anatomy,School of Basic Medical Science,Anhui Medical University,Hefei 230032;The Brain Science Center,Beijing Institute of Basic Medical Sciences,Beijing 100850)

机构地区：[1]安徽医科大学基础医学院人体解剖学教研室,合肥230032 [2]北京基础医学研究所脑科学中心,北京100850

出　　处：《安徽医科大学学报》2022年第10期1529-1535,共7页Acta Universitatis Medicinalis Anhui

基　　金：国家自然科学基金(编号:81930029)。

摘　　要：目的研究螺旋-环-螺旋手型结构域蛋白家族成员D 1/2(EFhd1/2)在阿尔茨海默病(AD)患者和模型小鼠中的表达差异。方法引用AD数据库(AlzData)中的数据信息,比较AD患者中EFhd1/2的表达变化;通过荧光定量PCR及Western blot检测AD患者与健康对照者脑组织中EFhd1/2的mRNA水平及蛋白水平变化;检测3月龄及6月龄AD模型小鼠及野生型小鼠脑组织中mRNA及蛋白表达变化;分离AD模型小鼠的小胶质细胞,通过RNA高通量测序(RNA-seq)检测小胶质细胞中EFhd1/2的变化。结果AD数据库数据分析显示,在转录水平上,AD患者EFhd1表达上升,而EFhd2则下降。AD患者脑组织样品检测显示,与健康对照者相比,AD患者不同脑区中EFhd1的表达均有上升趋势,而EFhd2则无差异。在AD小鼠模型中,与野生型小鼠相比,在3月龄及6月龄的AD模型小鼠中EFhd1的转录水平均无改变,但其蛋白水平上升;在3月龄AD模型小鼠中EFhd2的转录水平上升,在3月龄及6月龄的AD模型小鼠脑组织中EFhd2蛋白水平均无改变,但EFhd2在6月龄的AD模型小鼠的小胶质细胞中水平上升。结论在AD模型小鼠及AD患者脑组织中EFhd1水平均上升,提示EFhd1可能在AD发生发展中起到重要作用;而在AD模型小鼠的小胶质细胞中EFhd2水平上升,提示EFhd2在AD病理相关的小胶质细胞激活和神经炎症中可能发挥重要作用。Objective To investigate the expression differences of helix-loop-helix hand domain family member D 1/2(EFhd1/2)in Alzheimer′s disease(AD)patients and model mice.Methods The expression changes of EFhd1/2 in AD patients were compared by using data from Alzheimer′s disease database(AlzData),and the changes in mRNA levels and protein levels of EFhd1/2 in brain tissues of AD patients and healthy control group were detected by qPCR and Western blot.The changes of EFhd1/2 mRNA and protein expression in brain tissues of AD models and wild-type mice of 3-month-old and 6-month-old were detected.Microglia were isolated from AD models and detected the changes of EFhd1/2 by RNA-sequencing.Results The Analysis of Alzheimer′s Disease Database data showed that the mRNA levels of EFhd1 in AD patients increased,while EFhd2 decreased.AD patients brain tissue samples showed an upward trend in the expression of EFhd1 in different brain regions of AD patients compared with healthy controls,while EFhd2 was not different.In the AD mice model,the mRNA levels of EFhd1 were similar in both 3-month-old and 6-month-old AD mice compared with wild-type mice,but the protein levels of EFhd1 increased;the mRNA levels of EFhd2 increased in 3-month-old AD mice,and protein levels remained similar in the brain tissue from AD mice aged 3 months and 6 months.However,EFhd2 increased in microglia from 6-month-old AD mice.Conclusion EFhd1 increased in both AD model mice and brain tissue of AD patients,suggesting that EFhd1 might play an important role in the development of AD,while EFhd2 increased in microglia in AD model mice,indicating that EFhd2 might be involved in AD related microglia activation and neuroinflammation.

关 键 词：阿尔茨海默病 EFhd1 EFhd2 小胶质细胞 钙结合蛋白 

分 类 号：R749.16[医药卫生—神经病学与精神病学]