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采用 UHPLC-MS 的整合血浆和尿液代谢组学研究:淫羊藿对“肾阳虚证”大鼠的干预作用。

An integrated plasma and urinary metabonomic study using UHPLC-MS: intervention effects of Epimedium koreanum on 'Kidney-Yang Deficiency syndrome' rats.

机构信息

Department of Analytical Chemistry, Shenyang Pharmaceutical University, 103 Wenhua Road, Shenyang 110016, PR China.

出版信息

J Pharm Biomed Anal. 2013 Mar 25;76:200-6. doi: 10.1016/j.jpba.2012.12.022. Epub 2012 Dec 27.

DOI:10.1016/j.jpba.2012.12.022
PMID:23333940
Abstract

A metabonomic strategy based on UHPLC-MS with principal component analysis was developed to investigate the intervention effects of Epimedium koreanum on metabolism characters of 'Kidney-Yang Deficiency syndrome' rats. The rats were injected intraperitoneally hydrocortisone once daily for 15 days to simulate 'Kidney-Yang Deficiency syndrome' and then administered orally E. koreanum extract once daily for the following 15 days. Plasma and urine samples before hydrocortisone injection, on day 15 of hydrocortisone injection and on days 3, 6, 9, 12, 15 exposed to E. koreanum extract were collected. Significant metabolic disorders were observed in 'Kidney-Yang Deficiency syndrome' rats and sixteen potential biomarkers were identified. The disturbed plasma levels of phenylalanine, tryptophan, cholic acid, lysophosphatidylcholines and urinary levels of phenylalanine, hippurate, phenylacetylglycine, N(2)-succinyl-l-ornithine, creatinine, α-ketoglutarate, citrate, phenol sulfate, indoxyl sulfate, cresol sulfate in model rats were gradually restored to normal after administration of E. koreanum extract, which indicated that E. koreanum had time-dependent recovering effects via regulating oxidant-antioxidant balance, amino acid metabolism, lipid metabolism, energy metabolism, and gut microflora. This work highlights that metabonomics is a promising tool for studying the essence of Chinese medicine's syndrome theory and the action mechanism of traditional Chinese medicine, and provides scientific and reasonable information on safety and efficacy of traditional Chinese medicine.

摘要

基于 UHPLC-MS 结合主成分分析的代谢组学策略,用于研究淫羊藿提取物对“肾阳虚证”大鼠代谢特征的干预作用。将大鼠每天腹腔注射氢化可的松 15 天,模拟“肾阳虚证”,然后每天口服淫羊藿提取物 15 天。在注射氢化可的松前、第 15 天注射氢化可的松以及暴露于淫羊藿提取物第 3、6、9、12、15 天收集血浆和尿液样本。在“肾阳虚证”大鼠中观察到明显的代谢紊乱,并鉴定出 16 种潜在的生物标志物。模型大鼠的血浆中苯丙氨酸、色氨酸、胆酸、溶血磷脂酰胆碱和尿液中苯丙氨酸、马尿酸、苯乙酰甘氨酸、N(2)-琥珀酰-L-鸟氨酸、肌酐、α-酮戊二酸、柠檬酸、苯酚硫酸盐、吲哚硫酸盐、甲酚硫酸盐水平紊乱,经淫羊藿提取物给药后逐渐恢复正常,表明淫羊藿通过调节氧化应激平衡、氨基酸代谢、脂质代谢、能量代谢和肠道微生物群,具有时间依赖性的恢复作用。本工作强调了代谢组学是研究中药证候理论本质和中药作用机制的一种有前途的工具,并为中药的安全性和有效性提供了科学合理的信息。

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