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基于液质联用的尿代谢组学研究通心络对内皮功能障碍大鼠的影响

Effect of the traditional Chinese medicine tongxinluo on endothelial dysfunction rats studied by using urinary metabonomics based on liquid chromatography-mass spectrometry.

机构信息

CAS Key Laboratory of Separation Science for Analytical Chemistry, Dalian Institute of Chemical Physics, Chinese Academy of Sciences, 457 Zhongshan Road, Dalian 116023, China.

出版信息

J Pharm Biomed Anal. 2011 Aug 25;56(1):86-92. doi: 10.1016/j.jpba.2011.04.020. Epub 2011 Apr 27.

DOI:10.1016/j.jpba.2011.04.020
PMID:21620604
Abstract

A urinary metabonomic method based on ultra-fast liquid chromatography coupled with ion trap-time of flight mass spectrometry (UFLC/MS-IT-TOF) was employed to study the preventive efficacy and the metabolic changes caused by simavastatin and the traditional Chinese medicine tongxinluo in endothelial dysfunction rats. Principal component analysis (PCA) was applied to study metabolic patterns of endothelial dysfunction rats and healthy control rats. 1-Methyladenosine, indoxyl sulfate, hippuric acid, riboflavin, coproporphyrin, and p-cresol glucuronide were identified as potential biomarkers, indicating that pathways of adenine, tryptophan, phenylalanine, riboflavin and porphyrin metabolism were disturbed in endothelial dysfunction rats. Applications of simvastatin and tongxinluo to endothelial dysfunction rats improved endothelial function according to the results of histopathology and measurements of endothelin-1 and nitric oxide. Metabonomic studies suggested that tongxinluo prevents endothelial dysfunction by regulating multiple metabolic pathways to their normal state, whereas simvastatin only altered selected metabolic pathways. This research demonstrated that metabonomics is a powerful and promising tool for disease investigation and the efficacy evaluation of complex traditional Chinese medicines.

摘要

基于超快速液相色谱-离子阱飞行时间质谱联用技术(UFLC/MS-IT-TOF)的尿代谢组学方法被用于研究辛伐他汀和中药通心络对血管内皮功能障碍大鼠的预防作用及代谢变化。主成分分析(PCA)用于研究血管内皮功能障碍大鼠和健康对照组大鼠的代谢模式。鉴定出 1-甲基腺苷、吲哚硫酸、马尿酸、核黄素、粪卟啉和对羟基苯乙酸葡萄糖醛酸苷为潜在的生物标志物,表明血管内皮功能障碍大鼠的腺嘌呤、色氨酸、苯丙氨酸、核黄素和卟啉代谢途径受到干扰。辛伐他汀和通心络应用于血管内皮功能障碍大鼠,根据组织病理学和内皮素-1和一氧化氮测量结果改善了内皮功能。代谢组学研究表明,通心络通过调节多种代谢途径使其恢复正常状态来预防血管内皮功能障碍,而辛伐他汀仅改变了选定的代谢途径。本研究表明,代谢组学是一种强大而有前途的疾病研究和复杂中药疗效评价工具。

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