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

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

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GeneOntology(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。

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 miee at the same age were used as the control group. The lipid rafts of hippoeampus were extraeted from young and adult miee for analysis using high pefformanee liquid ehromatography-tandern mass speetrometry （HPLC-MS/MS）. The lipid raft proteome data were introdueed into DAVID bioinformaties analysis tool, then Gene Ontology （GO） analysis and Kyoto Eneyelopedia of Genes and Genomes （KEGG） analysis were earried out. The results of bioinformaties analysis were verified by mitoehondrial membrane potential and Morris water maze analysis. Results Compared with the eontrol miee of SAMR1, the aged SAMP8 miee showed obvious eognitive impairment. GO analysis showed that the mitoehondrial-related proteins deereased greatly in aged SAMP8 miee. KEGG analysis showed that the oxidative phosphorylation of mitoehondria was greatly reduced in the hippoeampus of SAMP8 miee. Mitoehondrial membrane potential analysis showed that the mitoehondrial membrane potential deereased signifieantly in the hippoeampus of aged SAMP8 miee. Conclusion During aging, the most eritieal cellular ehange in hippoeampus is the exeessive deeline of mitoehondrial oxidative phosphorylation, whieh may be an imporlant eellular meehanism of dementia in SAMP8 miee.