9.4T MRS观察阿尔茨海默病模型小鼠海马代谢物早期变化

摘要

Objective To assess the metabolite alteration in hippocampi of Alzheimer disease (AD) mice in vitro using 9. 4T high resolution magnetic resonance spectroscopy, and to observe the biomarkers of AD at early stage. Methods Thirty Kunming mice were randomly divided into experimental group (4 subgroups) and control group averagely. Mice of the experimental group were injected with D-galactose and NaNO2 respectively for 30, 40, 50 and 60 days, while of the control group was injected with saline for 60 days. Each mouse was subjected to the Morris water maze (MWM) test after injection. After MWM test, the mice were sacrificed and the hippocampi were taken out. The right hippocampi underwent 9. 4T ' H-MRS examination and the left hippocampi were stained for histopathology. Results The concentration of N-ace-gyl aspartate (NAA) was (30. 37±2. 88)^mol/L and glutamate (Glu) was (39. 98±4. 67)^mol/L in control group. The concentration of NAA and Glu decreased by 60. 36% and 72. 36% respectively on the 40-day subgroup compared to control group (P<0. 01). In 50-day subgroup, NAA and Glu concentrations both increased, but still remained lower than those of the control group. In 60-day subgroup, the concentrations of both metabolites decreased again. No difference was found for the concentrations of myo-inositol (ml) compared to the control group. MWM test showed a decrease of the spatial learning and memory at the last time point (P<0. 05). Histopathology confirmed the neuronal loss, amyloid plaques and neurofi-brillary tangles took place in the mice's hippocampi at 60-day subgroup. Conclusion ' H-MRS is a useful tool for observing the changing trend of metabolites. The decreased NAA and Glu may be biomarkers for early stage of AD.%目的 通过9.4T MRS离体检测阿尔茨海默病(AD)模型小鼠疾病过程中的代谢物变化,探讨MRS早期诊断此病的生物学标识.方法 将30只昆明小鼠随机平均分为实验组(4个亚组)和1个对照组,每组6只.对实验组小鼠分别连续注射D-半乳糖和亚硝酸钠30天、40天、50天及60天,对照组小鼠连续注射生理盐水60天,各组注射药物结束后行水迷宫测试并处死小鼠取其双侧海马.利用9.4T MRS观察右侧海马代谢物变化；对左侧海马行病理组织学染色.结果 MRS显示对照组N-乙酰天门冬氨酸(NAA)为(30.37±2.88)μmol/L,谷氨酸(Glu)为(39.98±4.67)μmol/L; 40天实验组亚组NAA及Glu分别较对照组降低60.36％和72.36％(p＜0.01)；50天亚组NAA及Glu较40天亚组有所升高,但仍低于对照组;60天亚组NAA及Glu再次降低.肌醇在对照组与实验组间变化无明显差异.水迷宫结果示60天亚组小鼠空间学习及记忆能力较对照组明显降低(P＜0.05).病理组织学染色示60天亚组小鼠海马神经元缺失、神经纤维缠结及老年斑形成.结论 MRS可检测AD病变过程中代谢物变化.NAA及Glu早期降低可能是早期诊断AD的生物学标识.