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一种高通量代谢组学方法,用于探究芒果苷对高脂血症大鼠代谢网络紊乱的调节作用。

A high-throughput metabolomic approach to explore the regulatory effect of mangiferin on metabolic network disturbances of hyperlipidemia rats.

作者信息

Zhou Chengyan, Li Gang, Li Yanchuan, Gong Liya, Huang Yifan, Shi Zhiping, Du Shanshan, Li Ying, Wang Maoqing, Yin Jun, Sun Changhao

机构信息

Development and Utilization Key Laboratory of Northeast Plant Materials of Liaoning Province, Department of Pharmacognosy, School of Traditional Chinese Materia Medica 48#, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenhe District, Shenyang 110016, China.

出版信息

Mol Biosyst. 2015 Feb;11(2):418-33. doi: 10.1039/c4mb00421c. Epub 2014 Nov 18.

DOI:10.1039/c4mb00421c
PMID:25406416
Abstract

This paper was designed to study metabolomic characters of the high-fat diet (HFD)-induced hyperlipidemia and the intervention effects of Mangiferin (MG). In this study, we aimed to investigate the intervention of MG on rats with hyperlipidemia induced by HFD and explore the possible mechanisms of hyperlipidemia. Urine metabolic profiles were analyzed using ultra-performance liquid chromatography/electrospray ionization quadruple time-of-flight mass spectrometry (UPLC-ESI-QTOF-MS) coupled with the principal component analysis (PCA) and partial least squares-discriminate analysis (PLS-DA) models, Heatmap and metabolism pathway analysis. PCA was applied to study the trajectory of the urinary metabolic phenotype of hyperlipidemia rat after administration of MG. The VIP-plot of orthogonal PLS-DA was used for discovering potential biomarkers to clarify the mechanism of MG. Biochemical analyses indicate that MG can alleviate the hyperlipidemia damage. Twenty significantly changed metabolites (potential biomarkers) were found to be reasonable in explaining the action mechanism of MG. The effectiveness of MG on hyperlipidemia is proved using the established metabolomic method and the regulated metabolic pathways involve the TCA cycle, taurine and hypotaurine metabolism, glyoxylate and dicarboxylate metabolism, glycine and serine and threonine metabolism, glycerophospholipid metabolism, primary bile acid biosynthesis etc. The results indicated that MG has a favourable protective effect on HFD-induced hyperlipidemia by adjusting the metabolic disorders. It also suggests that the metabolomic technology is a powerful approach for elucidation of the action mechanisms of MG.

摘要

本文旨在研究高脂饮食(HFD)诱导的高脂血症的代谢组学特征以及芒果苷(MG)的干预作用。在本研究中,我们旨在探讨MG对HFD诱导的高脂血症大鼠的干预作用,并探索高脂血症的可能机制。采用超高效液相色谱/电喷雾电离四级杆飞行时间质谱(UPLC-ESI-QTOF-MS)结合主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)模型、热图和代谢途径分析来分析尿液代谢谱。应用PCA研究MG给药后高脂血症大鼠尿液代谢表型的轨迹。采用正交PLS-DA的VIP图发现潜在生物标志物以阐明MG的作用机制。生化分析表明MG可减轻高脂血症损伤。发现20种显著变化的代谢物(潜在生物标志物)在解释MG的作用机制方面具有合理性。使用已建立的代谢组学方法证明了MG对高脂血症的有效性,其调节的代谢途径包括三羧酸循环、牛磺酸和低牛磺酸代谢、乙醛酸和二羧酸代谢、甘氨酸、丝氨酸和苏氨酸代谢、甘油磷脂代谢、初级胆汁酸生物合成等。结果表明MG通过调节代谢紊乱对HFD诱导的高脂血症具有良好的保护作用。这也表明代谢组学技术是阐明MG作用机制的有力方法。

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