APPswe小鼠β淀粉样斑块与胶质细胞激活相关性研究  

Correlation Study on the Roles of Glial Cell Activation in APPswe Mice

作　　者：段鸣锐 黄佩芝 欧官用 方州 沈辉帆 乔新宇 赵炜疆 DUAN Ming-rui;HUANG Pei-zhi;OU Guan-yong;FANG Zhou;SHEN Hui-fan;QIAO Xin-yu;ZHAO Wei-jiang(Center for Neuroscience,Shantou University Medical College,Shantou,Guangdong,515041,China;Cell Biology Department,Wuxi Medical College,Jiangnan University,Wuxi,Jiangsu,214122,China)

机构地区：[1]汕头大学医学院神经科学中心,广东汕头515041 [2]江南大学无锡医学院细胞生物学教研室,江苏无锡214122

出　　处：《现代生物医学进展》2021年第15期2819-2822,共4页Progress in Modern Biomedicine

基　　金：国家自然科学基金面上项目(81471279,81171138)。

摘　　要：目的:通过检测阿尔茨海默病(Alzheimer’s Disease,AD)APPswe转基因小鼠前额叶皮质(prefrontal cortex,PFC)中β-淀粉样蛋白(β-amyloid,Aβ)与胶质纤维酸性蛋白(glial fibrillary acidic protein,GFAP)和离子钙结合衔接分子1(Ionized calcium binding adaptor molecule-1,Iba-1)的表达相关性,进一步明确AD中β淀粉样斑块在神经胶质细胞激活中的重要作用。方法:选取9只12月龄APPswe AD小鼠,使用免疫组织化学法检测PFC中Aβ、GFAP以及Iba-1表达,并分析Aβ与GFAP和Iba-1水平的相关性;使用免疫荧光双标法分别评价不同大小Aβ斑块分别与GFAP和Iba-1的共染情况。结果:免疫组织化学结果显示,AD小鼠前额叶皮质中Aβ水平高,则GFAP和Iba-1信号水平也较高;反之,Aβ水平低,GFAP和Iba-1的表达水平也较低。Pearson相关性分析结果表明Aβ水平与GFAP(R=0.6677,P<0.05)和Iba-1(R=0.8257,P<0.05)的水平呈正相关,且与GFAP相比,Iba-1显示出与Aβ水平更高的表达相关性。与免疫组织化学结果一致,免疫荧光双标法结果亦表明小鼠PFC中较大的Aβ斑块所在区域GFAP或Iba-1荧光信号强度及范围亦大于较小的Aβ斑块所在区域GFAP或Iba-1荧光信号强度。结论:AD小鼠前额叶皮质中Aβ水平与GFAP和Iba-1的表达量呈正相关,表明Aβ形成在神经胶质细胞的激活中发挥重要作用。Objective:To verify the relationship betweenβ-amyloid(Aβ)plaques and glial cell activation by testing the correlation between Aβand glial fibrillary acidic protein(GFAP)or ionized calcium binding adaptor molecule-1(Iba-1)in the prefrontal cortex(PFC)of an Alzheimer’s Disease(AD)APPswe mouse model.Methods:Nine 12-month-old APPswe AD mice were included.The expression of Aβ,GFAP,and Iba-1 in the PFC was detected by immunohistochemistry,and the correlation of Aβwith either GFAP or Iba-1 level was analyzed.The co-existence of different sized Aβplaques with either GFAP or Iba-1 was detected by double-immunofluorescence labeling assay.Results:Immunohistochemical results showed that higher levels of Aβin the PFC of AD mice were associated with higher levels of GFAP and Iba-1.On the contrary,lower levels of Aβwere associated with lower levels of GFAP and Iba-1 expression.Pearson correlation analysis showed that Aβlevel was positively correlated with that of GFAP(R=0.6677,P<0.05)and Iba-1(R=0.8257,P<0.05),respectively.Immunofluorescence double labeling results also demonstrated that the region with large sized Aβplaques showed a higher fluorescence signal intensity of both GFAP and Iba-1 in the PFC of AD mice when compared to that with small sized Aβplaques.Conclusions:The level of Aβwas positively correlated with those of GFAP and Iba-1 in the PFC of AD mice,suggesting that Aβformation plays an important role in neuroinflammation induced by the activation of glial cells.

关 键 词：阿尔兹海默症 APPswe小鼠 β淀粉样斑块 神经炎症 GFAP Iba-1 

分 类 号：R749.16[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]