药学学报, 2021, 56(10): 2849-2857
引用本文:
王玲, 孙娥, 侯健, 徐金娣, 郭舒臣, 韦英杰, 贾晓斌. 基于UPLC-Q-TOF-MS代谢组学研究炙淫羊藿温肾助阳的炮制机制[J]. 药学学报, 2021, 56(10): 2849-2857.
WANG Ling, SUN E, HOU Jian, XU Jin-di, GUO Shu-chen, WEI Ying-jie, JIA Xiao-bin. The processing mechanism of epimedium fried with suet oil to warm kidney and enhance yang based on UPLC-Q-TOF-MS metabonomics[J]. Acta Pharmaceutica Sinica, 2021, 56(10): 2849-2857.

基于UPLC-Q-TOF-MS代谢组学研究炙淫羊藿温肾助阳的炮制机制
王玲1,2, 孙娥1,2*, 侯健2, 徐金娣1,2, 郭舒臣3, 韦英杰2, 贾晓斌3
1. 南京中医药大学第三临床医学院, 江苏 南京 210028;
2. 江苏省中医药研究院, 江苏 南京 210028;
3. 中国药科大学中药学院, 江苏 南京 211198
摘要:
采用代谢组学方法探究炙淫羊藿温肾助阳和炮制增效机制。建立氢化可的松诱导的大鼠肾阳虚证模型,基于UPLC-Q-TOF-MS (ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry)代谢组学方法,联合多元统计分析和单变量统计分析,筛选并鉴定血浆、尿液样品中与肾阳虚相关的潜在生物标志物,分析羊脂油组、淫羊藿生品组、淫羊藿加热品组、淫羊藿炙品组改善肾阳虚证的代谢调控机制。结果显示,氢化可的松诱导的肾阳虚大鼠血浆、尿液代谢呈现明显的轨迹变化,在血浆和尿液中鉴定出15种与肾阳虚相关的生物标志物,涉及5条代谢通路,分别为甘油磷脂代谢、鞘脂代谢、硫代谢、乙醛酸和二羧酸代谢、半胱氨酸和蛋氨酸代谢。炙淫羊藿温肾助阳的代谢通路涉及甘油磷脂代谢、半胱氨酸和蛋氨酸代谢,而炙淫羊藿两个炮制因素“加热”“羊脂油”分别通过调节甘油磷脂代谢、半胱氨酸和蛋氨酸代谢来增强其温肾助阳的作用,进而阐明了炙淫羊藿的炮制增效机制。本文涉及的动物实验符合伦理学标准,并且已获得江苏省中医药研究院动物伦理委员会批准(批准号:AEWC-20200702-119)。
关键词:    炙淫羊藿      炮制机制      代谢组学      肾阳虚证      UPLC-Q-TOF-MS      代谢通路     
The processing mechanism of epimedium fried with suet oil to warm kidney and enhance yang based on UPLC-Q-TOF-MS metabonomics
WANG Ling1,2, SUN E1,2*, HOU Jian2, XU Jin-di1,2, GUO Shu-chen3, WEI Ying-jie2, JIA Xiao-bin3
1. The Third Clinical Medical College, Nanjing University of Chinese Medicine, Nanjing 210028, China;
2. Jiangsu Province Academy of Traditional Chinese Medicine, Nanjing 210028, China;
3. School of Traditional Chinese Pharmacy, China Pharmaceutical University, Nanjing 211198, China
Abstract:
The metabonomics method was used to explore the processing and synergistic mechanism of epimedium fried with suet oil in warming the kidney and enhancing yang. The kidney-yang deficiency rat model was established by injection of hydrocortisone. Then the UPLC-Q-TOF-MS (ultra-performance liquid chromatography with quadrupole time-of-flight tandem mass spectrometry) metabolomics method was combined with multivariate statistical analysis methods and univariate statistical analysis to screen and identify kidney-yang deficiency potential biomarkers in plasma and urine samples. Finally the metabolic regulation mechanism of suet oil group, the epimedium raw product group, the epimedium heating product group, and the epimedium fried with suet oil group improved kidney-yang deficiency was analyzed. The results showed that the plasma and urine metabolism of rats with kidney-yang deficiency induced by hydrocortisone showed obvious trajectory changes. 15 biomarkers related to kidney-yang deficiency were identified in plasma and urine, involving 5 metabolic pathways, namely glycerophospholipid metabolism, sphingolipid metabolism, sulfur metabolism, glyoxylate acid and dicarboxylate metabolism, and cysteine and methionine metabolism. The metabolic pathway of epimedium fried with suet oil warming kidney and promoting yang involved glycerophospholipid metabolism, cysteine and methionine metabolism, and the two processing factors of epimedium fried with suet oil "heating" and "suet oil" enhanced its function of warming the kidney and promoting yang by regulating glycerophospholipid metabolism, cysteine and methionine metabolism, respectively. In this way, the processing and synergistic mechanism of epimedium fried with suet oil was clarified. The animal experiments involved in this article comply with ethical standards and have been approved by the Animal Ethics Committee of Jiangsu Provincial Academy of Chinese Medicine (approval number:AEWC-20200702-119).
Key words:    Epimedium fried with suet oil    processing mechanism    metabolomics    kidney-yang deficiency    UPLC-Q-TOF-MS    metabolic pathway   
收稿日期: 2021-04-01
DOI: 10.16438/j.0513-4870.2021-0481
基金项目: 国家自然科学基金资助项目(81503253,81573833);江苏省青年医学重点人才项目(QNRC2016635);南京中医药大学自然科学基金项目(XZR2020028);江苏省医学创新团队项目(CXTDB2017003);“重大新药创制”科技重大专项(2017ZX09301056);2021年江苏省研究生科研与实践创新计划项目(SJCX21-0715,SJCX21-0717).
通讯作者: 孙娥,Tel:86-25-52362109,E-mail:sune0825@163.com
Email: sune0825@163.com
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