Differential Metabolic Pathways and Metabolites in a C57BL/6J Mouse Model of Alcoholic Liver Disease

Differential Metabolic Pathways and Metabolites in a C57BL/6J Mouse Model of Alcoholic Liver Disease
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酒精性肝病 C57BL/6J 小鼠模型中的差异代谢途径和代谢物

DOI:
10.12659/msm.924602
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发表时间:
2020-05-08
影响因子:
3.1
通讯作者:
Xu, Long
Xu, Long
中科院分区:
医学4区
文献类型:
--
作者:
Ma, Tai;Li, Yue;Xu, Long

文献摘要

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背景资料:酒精性肝病(ALD)是急性或慢性肝损伤的重要原因,由酗酒或长期饮酒引起。迄今为止,还没有建立完善的小鼠模型,其具有模拟人类ALD的综合代谢特征。本研究旨在探讨酒精性肝病(ALD)小鼠模型肝脏中的差异代谢途径及相关的差异代谢产物。材料/方法:采用酒精灌胃10 d+酒精灌胃的方法建立C57 BU 6 J小鼠ALD模型。采用超高压液相色谱-四极杆飞行时间串联质谱法(UHPLC/Q-TOF-MS)检测ALD小鼠肝脏代谢物组学特征。这些代谢产物与多种代谢途径相关,包括嘌呤代谢、磷酸戊糖代谢、半胱氨酸和蛋氨酸代谢、D-谷氨酰胺和D-谷氨酸代谢、嘧啶代谢和维生素B6代谢。结论:本研究结果揭示了ALD潜在的生物标志物,为进一步了解ALD的发病机制提供了依据。
Background: Alcoholic liver disease (ALD), an important cause of acute or chronic liver injury, results from binge drinking or long-term alcohol consumption. To date, there is no well-established mouse model with a comprehensive metabolic profile that mimics ALD in humans. This study aimed to explore the differential metabolic pathways and related differential metabolites in the liver of an ALD mouse model.Material/Methods: A C57BU6J mouse model of ALD was induced by alcohol feeding for 10 days plus binge alcohol feeding. The metabolomic profiles in the liver of the ALD mouse model was detected through ultra-high-pressure liquid chromatography-quadrupole time-of-flight tandem mass spectrometry (UHPLC/Q-TOF-MS).Results: A total 35 metabolites were significantly altered during the development of ALD. These metabolites were cor-related to multiple metabolic pathways, including purine metabolism, the pentose phosphate pathway, cysteine and methionine metabolism, D-glutamine and D-glutamate metabolism, pyrimidine metabolism, and vitamin B6 metabolism.Conclusions: The findings of the present study reveal potential biomarkers of ALD, and provide further insights into the pathogenesis of ALD.