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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。

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

机构信息

School of Basic Medical Science, Anhui Medical University, Hefei, Anhui, China (mainland).

The First Affiliated Hospital of Anhui Medical University, Hefei, Anhui, China (mainland).

出版信息

Med Sci Monit. 2020 May 8;26:e924602. doi: 10.12659/MSM.924602.

Abstract

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 AND METHODS A C57BL/6J 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 correlated 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.

摘要

背景

酒精性肝病(ALD)是急性或慢性肝损伤的重要原因,由 binge drinking 或长期饮酒引起。迄今为止,尚无一种具有全面代谢特征的、可模拟人类 ALD 的小鼠模型。本研究旨在探索 ALD 小鼠模型肝脏中的差异代谢途径和相关差异代谢物。

材料和方法

通过连续 10 天酒精喂养和 binge 酒精喂养诱导 C57BL/6J 小鼠 ALD 模型。通过超高效液相色谱-四极杆飞行时间串联质谱(UHPLC/Q-TOF-MS)检测 ALD 小鼠模型肝脏中的代谢组学特征。

结果

在 ALD 的发展过程中,共有 35 种代谢物发生显著变化。这些代谢物与多种代谢途径相关,包括嘌呤代谢、戊糖磷酸途径、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 的潜在生物标志物,并为 ALD 的发病机制提供了更深入的认识。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/ec3b/7236594/0ee4100e6b72/medscimonit-26-e924602-g001.jpg

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