APP/PS1转基因AD小鼠脑内淀粉样斑块与铁沉积的磁敏感成像研究

The study of susceptibility weighted imaging of amyloid plaques and iron deposits in the brain of APP/PS1 transgenic AD mice

目的应用三维增强磁敏感成像(3D-enhanced susceptibility weighted angiography,ESWAN)技术检测APPswe/PSEN1de9基因突变型小鼠(购自美国Jackson Laboratory,简称为APP/PS1转基因小鼠)脑不同部位的平均相位值(mean phase value,MPV),并探讨其与铁蛋白及淀粉样斑块分布的相关性。材料与方法 APP/PS1转基因小鼠及野生型对照组小鼠行T1WI、T2WI和ESWAN序列扫描,测量小鼠脑皮质区、海马区及丘脑区MPV。对鼠脑组织进行铁蛋白和Aβ蛋白的免疫组化染色,并分别计数感兴趣区内染色斑块数量和面积所占百分比。对感兴趣区MPV与斑块数量、斑块面积百分比采用Pearson检验进行相关分析。结果 APP/PS1转基因小鼠与对照组小鼠皮质区(t=-2.201,P=0.045)和海马区(t=-2.524,P=0.024)的MPV值差异均具有统计学意义。APP/PS1转基因小鼠与对照组小鼠丘脑区的MPV差异不具有统计学意义(t=-2.094,P=0.055)。APP/PS1转基因小鼠每组中的MPV与铁蛋白斑块数量与范围分别具有显著相关性(P<0.05);淀粉样斑块与铁蛋白的数量与范围分别具有相关性(P<0.05)。结论 APP/PS1转基因小鼠脑内MPV与脑内铁沉积具有显著相关性。APP/PS1转基因小鼠脑内皮质区、海马区及丘脑区的铁沉积持续进行,并且与淀粉样斑块的形成具有相关性。

Objective:The aim is to apply the three dimensional enhanced magnetic sensitive imaging(3D-enhanced susceptibility weighted angiography,ESWAN)technology to detect APPswe/PSEN1de9 gene mutant mice(purchased from the United States Jackson that referred to as APP/PS1 transgenic mice)average phase values from different parts of the brain(mean phase value,MPV),and to explore its and ferritin and correlation of the distribution of amyloid plaques.Materials and Methods:APP/PS1 mutant mice and wild-type control mice underwent T1WI,T2WI and ESWAN sequence scanning to measure MPV in the cerebral cortex,hippocampus and thalamus of mice.Immunohistochemical staining of iron protein and Aβprotein in rat brain tissues was carried out,and the percentage of the number and area of stained plaques in the area of interest were counted respectively.Pearson correlation was used to analyze the MPV,patch number and patch area percentage in the ROI region.Results:The MPV values in the cortex area(t=-2.201,P=0.045)and hippocampal area(t=-2.524,P=0.024)of both APP/PS1 dual-transgenic mice and control mice were statistically different.There was no statistically significant difference in MPV between APP/PS1 dual transgenic mice and control mice in thalamus region(t=-2.094,P=0.055).The number and range of iron protein plaques and MPV in each group of APP/PS1 dual-transgenic mice were significantly correlated(P<0.05).The amount and range of amyloid plaques and ferritin were correlated(P<0.05).Conclusions:The mean phase value in the brain of transgenic mice with APP/PS1 was significantly correlated with iron deposition in the brain.The iron deposition in the cerebral cortex,hippocampus and thalamus continued in the APP/PS1 dual transgenic mice,and was associated with the formation of amyloid plaques.