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基于超高效液相色谱/四极杆飞行时间质谱联用技术结合模式识别方法和代谢通路分析的龙血竭对心肌缺血大鼠的代谢组学研究

Metabolomics Study of Resina Draconis on Myocardial Ischemia Rats Using Ultraperformance Liquid Chromatography/Quadrupole Time-of-Flight Mass Spectrometry Combined with Pattern Recognition Methods and Metabolic Pathway Analysis.

机构信息

Department of Pharmaceutical Analysis, School of Pharmacy, Second Military Medical University, 325 Guohe Road, Shanghai 200433, China ; Shanghai Key Laboratory for Pharmaceutical Metabolite Research, 325 Guohe Road, Shanghai 200433, China ; Shanghai Research Centre for Drug (Chinese Materia Medica) Metabolism, 325 Guohe Road, Shanghai 200433, China.

出版信息

Evid Based Complement Alternat Med. 2013;2013:438680. doi: 10.1155/2013/438680. Epub 2013 May 26.

Abstract

Resina draconis (bright red resin isolated from Dracaena cochinchinensis, RD) has been clinically used for treatment of myocardial ischemia (MI) for many years. However, the mechanisms of its pharmacological action on MI are still poorly understood. This study aimed to characterize the plasma metabolic profiles of MI and investigate the mechanisms of RD on MI using ultraperformance liquid chromatography/quadrupole time-of-flight mass spectrometry-based metabolomics combined with pattern recognition methods and metabolic pathway analysis. Twenty metabolite markers characterizing metabolic profile of MI were revealed, which were mainly involved in aminoacyl-tRNA biosynthesis, phenylalanine, tyrosine, and tryptophan biosynthesis, vascular smooth muscle contraction, sphingolipid metabolism, and so forth. After RD treatment, however, levels of seven MI metabolite markers, including phytosphingosine, sphinganine, acetylcarnitine, cGMP, cAMP, L-tyrosine, and L-valine, were turned over, indicating that RD is likely to alleviate MI through regulating the disturbed vascular smooth muscle contraction, sphingolipid metabolism, phenylalanine metabolism, and BCAA metabolism. To our best knowledge, this is the first comprehensive study to investigate the mechanisms of RD for treating MI, from a metabolomics point of view. Our findings are very valuable to gain a better understanding of MI metabolic profiles and provide novel insights for exploring the mechanisms of RD on MI.

摘要

龙血竭(从龙舌兰科龙血树中分离得到的鲜红色树脂,RD)临床上用于治疗心肌缺血(MI)已有多年。然而,其对 MI 的药理作用机制仍知之甚少。本研究旨在通过超高效液相色谱/四极杆飞行时间质谱联用代谢组学结合模式识别方法和代谢途径分析,对 MI 的血浆代谢谱进行特征描述,并研究 RD 对 MI 的作用机制。揭示了 20 个特征 MI 代谢谱的代谢标志物,主要涉及氨酰-tRNA 生物合成、苯丙氨酸、酪氨酸和色氨酸生物合成、血管平滑肌收缩、鞘脂代谢等。然而,RD 治疗后,7 种 MI 代谢标志物,包括植鞘氨醇、神经鞘氨醇、乙酰肉碱、cGMP、cAMP、L-酪氨酸和 L-缬氨酸的水平发生了变化,表明 RD 可能通过调节血管平滑肌收缩、鞘脂代谢、苯丙氨酸代谢和支链氨基酸代谢来缓解 MI。据我们所知,这是从代谢组学角度首次全面研究 RD 治疗 MI 的作用机制。我们的研究结果对于更好地了解 MI 的代谢谱非常有价值,并为探索 RD 治疗 MI 的机制提供了新的见解。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/78c0/3677627/0524d8920a0a/ECAM2013-438680.001.jpg

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