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投稿时间：2023-04-12
投稿时间：2023-04-12
中文摘要: 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。
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.
keywords: gangliosides monosialotetrahexosyl ganglioside（GM1） Alzheimer's disease APPswe/PSEN1dE9（APP/PS1） liquid chromatography-mass spectrometry（LC-MS）
文章编号：202319002 中图分类号： 文献标志码：
基金项目:国家重点研发计划项目（2018YFD0901101）；中央高校基本业务费项目（202012018）
| Author Name | Affiliation |
| LIU Bin，WANG Zhigao，WANG Xiaoxu，MA Yingxu，CONG Peixu，SONG Yu，XU Jie*，XUE Changhu | College of Food Science and Engineering，Ocean University of China，Qingdao 266003，Shandong，China |
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