【摘要】 目的探讨氢质子磁共振波谱(1H-MRS)成像对APP/PS1转基因AD小鼠代谢变化的显示及其早期诊断价值。方法35只APP/PS1AD小鼠(实验组)和20只同源野生型小鼠(对照组)在6、9月龄时接受Morris水迷宫测试及1H-MRS成像。1H-MRS测量小鼠大脑海马区N-乙酰天门冬氨酸(NAA)、肌醇(mI)和肌酸(Cr)的峰下面积,计算NAA/Cr和mI/Cr比值并进行两样本均数t检验。结果与对照组比较,实验组小鼠6月龄时mI/Cr比值明显升高(t=2.904,P<0.05),NAA/Cr比值明显降低(t=-7.535,P<0.05)。免疫组化检查显示海马区出现Aβ沉积斑块,周围包绕活化的胶质细胞;而行为学差异在9月龄时才有统计学意义(P<0.05),表现为小鼠学习和记忆方面的损害。结论1H-MRS是早期评价AD的高敏感性、高特异性的方法,mI、NAA的变化早于行为学改变。更多还原

【Abstract】 Objective To explore the value of 1H-MR spectroscopy (1H-MRS) in displaying changes of metabolites and in the diagnosis of AD in early stage in APP/PS1 double transgenic Alzheimer’s disease (AD) mice. Methods Study of behavior and 1H-MRS was performed in 35 APP/PS1 AD mice (study group) and 20 homologous wild type mice (control group) at 6 and 9 months of age. Behavioral detection test learning and memory capacity of mice were assessed through Morris water maze. For 1H-MRS,sub-peak areas of N-acetyl aspartate (NAA),myo-inositol (mI) and creatinine (Cr) in the cerebral cortex and hippocampus were measured,and the NAA/Cr and mI/Cr ratios were calculated and compared with the two-sample t-test. Results Compared with the control group,the mI/Cr ratio of the 6-month-old AD mice significantly increased (t=2.904,P<0.05),and the NAA/Cr ratio significantly decreased (t=-7.535,P<0.05). Immunohistochemistry of the hippocampus demonstrated the appearance of Aβ plaque deposition and the activated astrocyte surrounded the plaque. However,there were significant differences in behavioral detection at 9 months of age (P<0.05),indicating damage in learning and memory of AD mice. Conclusion 1H-MRS is a method for early assessment of AD with high sensitivity and specificity,and change of mI and NAA happen prior to behavior in APP/PS1 double transgenic AD mice.更多还原