快速老化小鼠SAMP8模型粪便代谢物和肠道菌群改变的研究  

Fecal metabolome and gut microbiome alterations in a mouse model of senescence accelerated mouse prone 8(SAMP8)

作　　者：李佳琪 高丽[1] 王珂欣 周玉枝[1] 秦雪梅[1] 杜冠华[3] LI Jia-qi;GAO Li;WANG Ke-xin;ZHOU Yu-zhi;QIN Xue-mei;DU Guan-hua(Modem Research Center for Traditional Chinese Medicine, Shanxi University, Taiyuan 030006, China;College of Chemistry and Chemical Engineering, Shanxi University, Taiyuan 030006, China;Institute of Materia Medica, Chinese Academy of Medical Science and Peking Union Medical College, Beijing 100050, China)

机构地区：[1]山西大学中医药现代研究中心,山西太原030006 [2]山西大学化学化工学院,山西太原030006 [3]中国医学科学院北京协和医学院药物研究所,北京100050

出　　处：《中草药》2018年第10期2265-2273,共9页Chinese Traditional and Herbal Drugs

基　　金：国家自然科学青年基金资助项目(81603319);山西省高等学校科技创新项目(2015118);山西省科技创新重点团队支柱项目(201605D131045-18);地产中药功效物质研究与利用山西省重点实验室项目(201605D111004)

摘　　要：目的研究快速老化小鼠SAMP8模型老化过程中粪便代谢物和肠道菌群的变化。方法采用1H-NMR代谢组学和宏基因组学技术,探索衰老相关的代谢标志物和肠道菌群,并对代谢物与肠道菌群进行Pearson关联分析。结果 SAMP8小鼠粪便中指认出31种内源性代谢物,与SAMR1小鼠相比,13种代谢物发生显著改变。差异代谢物主要富集在4条代谢途径:苯丙氨酸、酪氨酸和色氨酸的生物合成,缬氨酸、亮氨酸和异亮氨酸的生物合成,苯丙氨酸代谢,组氨酸代谢。肠道菌群分析发现10月龄快速老化小鼠SAMP8肠道菌群多样性明显改变,10种菌群的相对丰度显著改变。相关性分析结果表明,Christensenellaceae菌科与苯丙氨酸、组氨酸、缬氨酸、异亮氨酸和尿苷酸均呈正相关;Dehalobacterium菌属与酪氨酸,Planococcaceae动球菌科与缬氨酸均呈负相关。结论通过研究快速老化小鼠SAMP8模型粪便代谢物和菌群的变化规律,为衰老机制及抗衰老药物研究提供实验依据。Objective To investigate the alterations of fecal metabolites and intestinal flora during the aging in a mouse model of senescence accelerated mouse prone 8（SAMP8）. Methods The 1 H-NMR metabonomics and metagenomics were applied to investigate the aging-related metabolic markers and intestinal flora, and Pearson correlation analysis was performed between metabolites and gut flora. Results Thirty-one endogenous metabolites were identified in the faeces of SAMP8 mice, of which 13 metabolites changed significantly compared with SAMR1 mice. Differential metabolites were mainly enriched in four metabolic pathways： phenylalanine, tyrosine and tryptophan biosynthesis; valine, leucine and isoleucine biosynthesis; phenylalanine metabolism; histidine metabolism. The results showed that the diversity of intestinal flora was significantly changed and the relative abundances of 10 kinds of intestinal flora were significantly changed in 10-month-old SAMP8 mice. Correlation analysis showed that Christensenellaceae was positively correlated with phenylalanine, histidine, valine, isoleucine, and uridylic acid; Dehalobacterium was negatively correlated with tyrosine, and Planococcaceae was negatively correlated with valine. Conclusion This paper reveals the changes of fecal metabolites and gut flora in SAMP8 mice, which provides experimental evidence for the study of aging progress and anti-aging actions of drugs.

关 键 词：快速老化小鼠 SAMP8 肠道菌群 代谢组学 宏基因组学 

分 类 号：R965.1[医药卫生—药理学]