阿尔茨海默病转基因模型Tg2576小鼠血清的代谢组学研究

发布时间：2018-03-31 07:36

本文选题：阿尔茨海默病　切入点：Tg小鼠　出处：《中国实验动物学报》2017年02期

【摘要】：目的 Tg2576转基因小鼠与阿尔茨海默病(Alzheimer’s disease,AD)患者的病理改变相近,本文动态研究了Tg2576小鼠在AD发病不同阶段的血清代谢物特征,为临床AD的早期诊断提供代谢依据。方法收集Tg2576小鼠在AD发病初期(6个月)和末期(12个月)时的血清样本,采集样本的1HNMR谱并运用多变量分析方法进行代谢特征的分析。结果结果显示Tg2576与C57小鼠分别在6和12个月时的血清代谢特征有明显差异,且不同AD发病阶段的Tg2576小鼠具有明显的代谢差异。与C57小鼠相比,在AD出现的初期阶段,Tg2576小鼠血清中乳酸、肌醇和氨基酸(如亮氨酸、异亮氨酸、丙氨酸)的含量升高,而脂质、胆碱、磷脂酰胆碱/甘油磷脂酰胆碱、甜菜碱、甘氨酸和葡萄糖含量降低;在AD发病的末期,血清中乳酸、肌醇和丙氨酸的含量继续上升,脂质、胆碱、磷脂酰胆碱/甘油磷脂酰胆碱、甜菜碱和甘氨酸含量持续降低,同时谷氨酸和肌酸含量初步显示出下降趋势。通过比较AD的初期和末期血清代谢物,我们能够发现疾病末期血清中乳酸、肌醇和丙氨酸含量升高,脂质、胆碱、磷脂酰胆碱、甘油磷脂酰胆碱含量降低。在这些代谢物中,乳酸、脂质、胆碱、磷脂酰胆碱和甘油磷脂酰胆碱在AD发生初期已具有显著性变化,且与AD发生的严重程度密切相关。结论结果表明Tg2576小鼠中乳酸与阿尔茨海默病程度的加重呈正相关变化,而脂质、胆碱、磷脂酰胆碱和甘油磷脂酰胆碱呈负相关改变,且这些代谢物随着疾病的发展呈动态进行性变化,可能是AD早期诊断的重要代谢标志物。
[Abstract]:Objective the pathological changes of Tg2576 transgenic mice were similar to those of patients with Alzheimer's disease (AD). The characteristics of serum metabolites in Tg2576 mice at different stages of AD were dynamically studied. Methods Serum samples of Tg2576 mice were collected at the beginning (6 months) and the final stage (12 months) of AD. The 1HNMR spectra of the samples were collected and the metabolic characteristics were analyzed by multivariate analysis. The results showed that the serum metabolic characteristics of Tg2576 and C57 mice were significantly different from those of C57 mice at 6 and 12 months, respectively. Compared with C57 mice, the levels of lactic acid, inositol and amino acids (such as leucine, isoleucine, alanine) in the serum of Tg2576 mice were higher than those in C57 mice. The contents of lipid, choline, phosphatidylcholine / glycerophosphatidylcholine, betaine, glycine and glucose decreased, and the contents of lactic acid, inositol and alanine in serum continued to increase at the end of AD. The contents of phosphatidylcholine / glycerophosphatidylcholine, betaine and glycine continued to decrease, while the contents of glutamate and creatine showed a decreasing trend. We can find that the levels of lactic acid, inositol and alanine increase in the serum at the end of the disease, and the levels of lipid, choline, phosphatidylcholine, glycerophosphatidylcholine decrease in these metabolites, lactic acid, lipid, choline, Phosphatidylcholine and glycerol phosphatidylcholine had significant changes in the early stage of AD and were closely related to the severity of AD. Conclusion the results showed that lactic acid in Tg2576 mice was positively correlated with the severity of Alzheimer's disease. However, lipid, choline, phosphatidylcholine and glycerophosphatidylcholine were negatively correlated, and these metabolites showed dynamic and progressive changes with the development of the disease, which may be an important metabolic marker for early diagnosis of AD.
【作者单位】：广东药科大学基础学院;
【基金】：广东省科技计划项目(编号:2016A030303062)
【分类号】：R749.16;R-332

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