【摘要】 为探究外源单唾液酸四己糖神经节苷脂（monosialotetrahexosyl ganglioside,GM₁）对阿尔兹海默症（Alzheimer’s disease,AD）小鼠内源性神经节苷脂（gangliosides,GLS）代谢的调控作用。采用淀粉样蛋白和人早老蛋白1（APPswe/PSEN1dE9,APP/PS1）双转基因小鼠作为AD模型，首先利用Morris水迷宫观测摄食GM₁对APP/PS1小鼠行为学的影响；进而利用液相色谱-质谱法（liquid chromatography-mass spectrometry,LC-MS）分析GM₁对APP/PS1小鼠脑皮质中GLS总体水平及各亚类水平的影响，采用多元统计分析探究GLS分子种变化。最后利用实时荧光定量聚合酶链式反应（real-time quantitative polymerase chain reaction,RT-qPCR）检测GLS合成与分解基因的mRNA表达。结果表明，GM₁能够改善APP/PS1小鼠的空间学习与记忆能力、提高脑皮质中GLS总含量、回调APP/PS1小鼠脑皮质中GLS各亚类含量。摄食GM₁能够显著上调GLS合成基因（st3gal5p1、st8sia1、b3galt4、st3gal2和soat）的mRNA表达水平，下调GLS分解基因hexa的mRNA表达水平。综上，膳食GM₁可以调控AD小鼠脑内GLS的代谢。更多还原

【Abstract】 The regulatory effect of exogenous monosialotetrahexosyl ganglioside（GM₁）on the metabolism of endogenous gangliosides（GLS） was investigated in the Alzheimer’s disease（AD） model established with APPswe/PSEN1dE9（APP/PS1）double transgenic mice. Morris water maze was designed to examine the behaviors of the APP/PS1 mice. Further,liquid chromatography-mass spectrometry（LC-MS）was employed to measure the overall level of GLS and the level of each subclass in the cerebral cortex of APP/PS1 mice. Multivariate statistical analysis was performed to explore the changes in GLS molecular species. Finally,real-time quantitative polymerase chain reaction（RT-qPCR）was employed to determine the mRNA levels of the genes involved in GLS synthesis and catabolism. The results showed that GM₁ improved the spatial learning and memory ability,elevated the total GLS level,and modulated the levels of GLS subclasses in the cerebral cortex of APP/PS1 mice. The ingestion of GM₁ significantly up-regulated the mRNA levels of the genes（st3gal5p1,st8sia1,b3galt4,st3gal2,and soat）involved in GLS synthesis and down-regulated the mRNA levels of hexa associated with GLS catabolism. In conclusion,dietary GM₁ can regulate the metabolism of endogenous GLS in the brain of AD mice.更多还原