天津医药

天津医药 ›› 2018, Vol. 46 ›› Issue (10): 1050-1054.doi: 10.11958/20180800

• 实验研究 • 上一篇    下一篇

脂筏蛋白质组学分析揭示快速老化因素对SAMP8 小鼠海马组织的关键影响

张雪竹，付于，贾玉洁，韩景献，聂坤△   

  1. 基金项目：国家自然科学基金资助项目（81574049） 作者单位：天津中医药大学第一附属医院（邮编300193） 作者简介：张雪竹（1972），女，博士，研究员，主要从事脑血管病的机制研究 △通讯作者 E-mail: kuntas2013@163.com
  • 收稿日期:2018-05-18 修回日期:2018-07-30 出版日期:2018-10-15 发布日期:2018-11-09
  • 通讯作者: 聂坤 E-mail:kuntas2013@163.com
  • 基金资助:
    基于LINCS网络集成式公共数据库研究针刺对海马突触可塑性的影响及 “细胞应激”相关机制

Proteomic analysis of lipid rafts reveals the key effects of the accelerated-aging on hippocampus in SAMP8 mice

ZHANG Xue-zhu, FU Yu, JIA Yu-jie, HAN Jing-xian, NIE Kun△   

  1. The First Teaching Hospital of Tianjin University of Traditional Chinese Medicine, Tianjin 300193, China △Corresponding Author E-mail: kuntas2013@163.com
  • Received:2018-05-18 Revised:2018-07-30 Published:2018-10-15 Online:2018-11-09
  • Contact: NIE Kun E-mail:kuntas2013@163.com
  • Supported by:
    Study on the effect of acupuncture on hippocampal synaptic plasticity based on LINCS network integrated public database and the mechanism of "cell stress"

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摘要： 摘要：目的 探讨快速老化小鼠SAMP8老年性痴呆的关键细胞学机制。方法 以2月龄和8月龄SAMP8小鼠 各40只为痴呆相关快速老化动物模型，以同月龄各40只正常老化小鼠SAMR1为对照，从小鼠海马组织提取脂筏蛋 白，采用高效液相色谱-串联质谱法分析。脂筏蛋白质组学检测数据导入DAVID生物信息学分析工具，进行Gene Ontology（GO）生物信息学分析和Kyoto Encyclopedia of Genes and Genomes（KEGG）代谢网络分析，并用线粒体膜电位 和Morris水迷宫方法验证生物信息学分析结果。结果 与SAMR1小鼠比较，快速老化的SAMP8小鼠出现明显的认 知障碍。GO 分析显示，老年期 SAMP8 小鼠脂筏蛋白组中线粒体相关蛋白大幅度减少。KEGG 分析显示，老年期 SAMP8小鼠海马组织线粒体的氧化磷酸化功能大幅度衰退。线粒体膜电位分析显示，老年期SAMP8小鼠海马组织 线粒体膜电位大幅度降低。结论 在老化过程中，SAMP8小鼠海马组织最关键的细胞变化是线粒体氧化磷酸化功 能的过度衰退，这可能是其痴呆发生的重要细胞学机制。

关键词: 阿尔茨海默病, 衰老, 过早, 细胞衰老, 氧化磷酸化, 线粒体

Abstract: Abstract: Objective To explore the key cytological mechanism of Alzheimer’s disease in SAMP8 mice. Methods Two-month-old and 8-month-old SAMP8 mice were used as the accelerated-aging model of dementia, and 40 SAMR1 mice at the same age were used as the control group. The lipid rafts of hippocampus were extracted from young and adult mice for analysis using high performance liquid chromatography-tandern mass spectrometry (HPLC-MS/MS). The lipid raft proteome data were introduced into DAVID bioinformatics analysis tool, then Gene Ontology (GO) analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) analysis were carried out. The results of bioinformatics analysis were verified by mitochondrial membrane potential and Morris water maze analysis. Results Compared with the control mice of SAMR1, the aged SAMP8 mice showed obvious cognitive impairment. GO analysis showed that the mitochondrial-related proteins decreased greatly in aged SAMP8 mice. KEGG analysis showed that the oxidative phosphorylation of mitochondria was greatly reduced in the hippocampus of SAMP8 mice. Mitochondrial membrane potential analysis showed that the mitochondrial membrane potential decreased significantly in the hippocampus of aged SAMP8 mice. Conclusion During aging, the most critical cellular change in hippocampus is the excessive decline of mitochondrial oxidative phosphorylation, which may be an important cellular mechanism of dementia in SAMP8 mice.

Key words: Alzheimer disease, aging, premature, cell aging, oxidative phosphorylation, mitochondria