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钩藤散改善APP/PS1双转基因小鼠学习记忆功能的代谢组学研究 被引量:1

The Metabolomic Study of Learning and Memory Function of APP/PS1 Double Transgenic Mice Improved by Gouteng San
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摘要 目的:采用非靶向的高通量尿液代谢组学技术对钩藤散改善淀粉样前体蛋白/早老素蛋白1基因,即APP/PS1双转基因小鼠的作用机制进行研究。方法:5月龄APP/PSI小鼠采用Morris水迷宫实验检测双转基因小鼠的空间学习能力,在确定出现空间记忆能力功能损伤地条件下采用基于非靶向的尿液代谢组学技术研究APP/PSI小鼠的代谢网络,聚焦关键通路,同时观察钩藤散在水迷宫和代谢水平上的治疗作用。结果:Morris水迷宫对比发现APP/PSI小鼠的空间记忆能力明显长于同窝野生小鼠,给予钩藤散后呈现一定程度的回调趋势,经非靶向的代谢轮廓分析和核心代谢通路聚焦后,成功发现正常小鼠(同窝野生小鼠)和APP/PSI双转基因小鼠代谢轮廓间差异最大的信号,经质谱解析和权威数据库检索后鉴定6个与学习记忆相关的潜在生物标记物,分别是牛磺酸(taurine)、叶酸(pteroylglutamic acid)、新蝶呤(neopterin)、磺乙谷酰胺(glutaurine)、戊邻酮二酸盐(2-oxoglutarate)、二氢新蝶呤(dihydroneopterin),他们主要涉及牛磺酸代谢及叶酸代谢等,经钩藤散治疗后能有效回调。结论:钩藤散对APP/PSI双转基因小鼠的学习记忆能力具有一定治疗作用,本次发现的6个生物标记物可能是APP/PSI双转基因小鼠发病的潜在靶点,为钩藤散的相关药效学研究提供实验依据。 Objective: The non targeted high-throughput urine metabolomlcs technology was used to study the pathogenesls ot APP/PS1 double transgenic mice and the mechanism of action of Gouteng san. Methods: 5-month-old APP/PS1 double transgenic mice were test with Morris water maze for spatial learning ability. Then we employed the non targeted high-throughput urine metabolomics technology to study the pathogenesis of APP/PS 1 double transgenic mice based on the metabolic network. The focus investigation of the key pathways and the observation of the treatment by Morris water maze and metabolic level have been used after spatial learning ability damaged confirmed. Results: The comparison between APP/PS1 double transgenic mice and normal mice suggested that a significant longer was existed in former, which was call-back by Gouteng san. With the non targeted high-throughput urine metabolomics analysis and pathway focused analysis, we found certain signals from metabolic profiling, which was identified to be 6 biomarkers associated with learning and memory function by mass spectrometry analysis or authoritative database. Respectively, they were taurine, pteroylglutamic acid, neopterin, glutaurine, 2-oxoglutarate and dihydroneopterin. They were mainly related to taurine metabolism and folate metabolism and represented an effective callback. Conclusion: Gouteng san possess a favorable effect on learning and memory ability of APP/PS1 double transgenic mice, 6 biomarkers may be a potential target for the pathogenesis of APP/PSI double transgenic mice and provide experimental basis for the study of Gouteng san.
出处 《现代生物医学进展》 CAS 2017年第23期4416-4420,共5页 Progress in Modern Biomedicine
基金 国家自然科学基金项目(81373777 81173599)
关键词 钩藤散 APP/PS1双转基因小鼠 MORRIS水迷宫 代谢组学 潜在靶点 Gouteng san APP/PS 1 transgenic mice Morris water maze Metabolomics Potential target
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  • 1王跃春.Y型电迷宫在大鼠学习记忆功能测试中的合理运用[J].中国行为医学科学,2005,14(1):69-70. 被引量:61
  • 2李国营,汪华侨,胡金家,徐杰,姚志彬.AD转基因模型Tg2576鼠阳性子鼠的病理和认知行为变化[J].神经解剖学杂志,2006,22(4):384-388. 被引量:7
  • 3Hsiao K,Borchelt D R,Olson K,et al.Age-related CNS disorderand early death in transgenic FVB/N mice overexpressing Alzheimeramyloid precursor proteins[J].Neuron,1995,15(5):1203.
  • 4Van Leuven F.Single and multiple transgenic mice as models forAlzheimer's disease[J].Prog Neurobiol,2000,61(3):305.
  • 5Morris R.Developments of a water-maze procedure for studyingspatial learning in the rat[J].Neurosci Methods,1984,11(1):47.
  • 6Goat A,Chartier-Harlin C M,Mullah M,et al.Segregation of amissense mutation in the amyloid precursor protein gene with familialAlzheimer's disease[J].Nature,1991,349(6311):704.
  • 7Savonenko A,Xu G M,Melnikova T,et al.Episodic-likememory deficits in the APPswe/PS1dE9 mouse model of Alzheimer'sdisease:relationships to beta-amyloid deposition andneurotransmitter abnormalities[J].Neurobiol Dis,2005,18(3):602.
  • 8Nicholls J A,Wilkinson D,Holmes C,et al.Neuropathology of human Alzheimer's disease after immunization with amyloid beta-peptide:a case report[J].Nat Med,2003,9(4):448.
  • 9Bell K F,Claudio Cuello A.Altered synaptic function inAlzheimer's disease[J].Eur J Pharmacol,2006,545(1):11.
  • 10Gordon MN, King DL, Diamond DM et al. Correlation between cognitive deficits and Aβ deposits in transgenic APP/PS1 mice. Neurobiol Aging, 2001 ;22:377 - 386

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