基于 LC-MS 的冠心病人源菌群小鼠代谢组学研究
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卫健委人类疾病比较医学重点实验室,中国医学科学院医学实验动物研究所,北京协和医学院比较医学中心, 北京 100021

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Metabolic analysis of human flora-associated mice with coronary heart disease using liquid chromatography-mass spectrometry
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Key Laboratory of Human Disease Comparative Medicine,Ministry of Health, Institute of Laboratory Animal Science, Chinese Academy of Medical Sciences (CAMS) Comparative Medical Center, Peking Union Medical College (PUMC), Beijing 100021, China

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    摘要:

    目的 使用基于液态色谱-质谱联用法( liquid chromatography-mass spectrometry,LC-MS)的非靶向代 谢组学技术研究冠心病人源菌群小鼠特征性代谢产物。 方法 28 只无菌雌性 C57BL/ 6J 小鼠分为对照组(CON) 和模型组(CAD),分别接种健康志愿者和冠心病患者的新鲜粪便悬液,移植后 6 周和 10 周每组安乐 7 只动物采集 血浆, 使用 LC-MS 技术对小鼠的血浆代谢物进行研究,运用 PCA 和 PLS-DA 统计学方法鉴别特征代谢物及相关代 谢通路。 结果 最终通过标准品确认 30 个在 2 个时间点均存在的特征性差异代谢物。 其中 L-肉毒碱、苯丙酮酸、 1-萘酚、2-萘酚在模型组显著升高。 胆汁酸代谢通路、甘氨酸丝氨酸和苏氨酸代谢途径在建模 6 周、10 周均下调。 结论 冠心病人源菌群小鼠出现与患者类似的代谢紊乱。

    Abstract:

    Objective To use liquid chromatography-mass spectrometry based plasma metabonomics to study the characteristics of human flora-associated (HFA) mice with coronary heart disease. Methods Twenty-eight female germ free C57BL/ 6J mice were divided into healthy control and coronary heart disease (CAD) groups. Each mouse was orally inoculated with a stool suspension from healthy people or patients with CAD to establish the HFA mouse models. At 6 and 10 weeks after inoculation, plasma metabolites were studied and PCA and PLS-DA statistical method were used to identify the characteristic metabolites. Results The PCA, PLS-DA and variable importance in projection analysis identified 30 characteristic metabolites present at 6 and 10 weeks after inoculation; structural identification found that L-carnitine, phenylpyruvic acid, and 1-naphthol, 2-naphthol were significantly higher in the CAD group compared with the control group. These potential biomarkers were related to the bile acid pathway and glycine, serine, threonine pathway. Conclusions The metabolism disorder in HFA mice appears similar to that of patients with CAD.

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朱华,郭亚茜,杜晓鹏,李卓,苏磊,秦川.基于 LC-MS 的冠心病人源菌群小鼠代谢组学研究[J].中国实验动物学报,2020,28(3):323~329.

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  • 收稿日期:2019-12-11
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  • 在线发布日期: 2020-07-03
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