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一种用于研究雷公藤致肝损伤的综合脂质组学分析方法的建立与应用

Development and application of a comprehensive lipidomic analysis to investigate Tripterygium wilfordii-induced liver injury.

作者信息

Xie Tong, Zhou Xueping, Wang Shouchuan, Lu Yan, Zhu Huaxu, Kang An, Deng Haishan, Xu Jianya, Shen Cunsi, Di Liuqing, Shan Jinjun

机构信息

Jiangsu Key Laboratory of Pediatric Respiratory Disease, Institute of Pediatrics, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.

The First Clinical College, Nanjing University of Chinese Medicine, Nanjing, Jiangsu, 210023, China.

出版信息

Anal Bioanal Chem. 2016 Jun;408(16):4341-55. doi: 10.1007/s00216-016-9533-9. Epub 2016 Apr 16.

DOI:10.1007/s00216-016-9533-9
PMID:27086014
Abstract

Lipid metabolic pathways play pivotal roles in liver function, and disturbances of these pathways are associated with various diseases. Thus, comprehensive characterization and measurement of lipid metabolites are essential to deciphering the contributions of lipid network metabolism to diseases or its responses to drug intervention. Here, we report an integrated lipidomic analysis for the comprehensive detection of lipid metabolites. To facilitate the characterization of untargeted lipids through fragmentation analysis, nine formulas were proposed to identify the fatty acid composition of lipids from complex MS (n) spectrum information. By these formulas, the co-eluted isomeric compounds could be distinguished. In total, 250 lipids were detected and characterized, including diacylglycerols, triacylglycerols, glycerophosphoethanolamines, glycerophosphocholines, glycerophosphoserines, glycerophosphoglycerols, glycerophosphoinositols, cardiolipins, ceramides, and sphingomyelins. Integrated with the targeted lipidomics, a total of 27 inflammatory oxylipins were also measured. To evaluate the aberrant lipid metabolism involved in liver injury induced by Tripterygium wilfordii, lipid network metabolism was further investigated. Results indicated that energy lipid modification, membrane remodeling, potential signaling lipid alterations, and abnormal inflammation response were associated with injury. Because of the important roles of lipids in liver metabolism, this new method is expected to be useful in analyzing other lipid metabolism diseases.

摘要

脂质代谢途径在肝功能中起关键作用,这些途径的紊乱与多种疾病相关。因此,对脂质代谢物进行全面表征和测量对于解读脂质网络代谢对疾病的贡献或其对药物干预的反应至关重要。在此,我们报告了一种用于全面检测脂质代谢物的综合脂质组学分析方法。为了通过碎片分析促进对非靶向脂质的表征,我们提出了九个公式,用于从复杂的质谱(n)谱信息中识别脂质的脂肪酸组成。通过这些公式,可以区分共洗脱的同分异构体化合物。总共检测并表征了250种脂质,包括二酰基甘油、三酰基甘油、甘油磷酸乙醇胺、甘油磷酸胆碱、甘油磷酸丝氨酸、甘油磷酸甘油、甘油磷酸肌醇、心磷脂、神经酰胺和鞘磷脂。结合靶向脂质组学,还测量了总共27种炎性氧化脂质。为了评估雷公藤诱导的肝损伤中涉及的异常脂质代谢,我们进一步研究了脂质网络代谢。结果表明,能量脂质修饰、膜重塑、潜在信号脂质改变和异常炎症反应与损伤有关。由于脂质在肝脏代谢中的重要作用,这种新方法有望用于分析其他脂质代谢疾病。

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