代谢组学及其研究新进展

摘要/Abstract

摘要： 代谢组学是研究生物体受刺激（如病理生理刺激）或被扰动后（如基因变异、蛋白修饰、环境变化）其代谢物种类、数量及其变化规律的科学。近几年来，代谢组学已经成为生命科学领域一个重要的组学技术，主要应用在药物毒理学研究、疾病诊断、中药等领域。本文综合国内外文献报道，介绍当前代谢组学研究中样品制备、仪器分析技术、数据处理方法和应用的最新研究概况，并对代谢组学的发展趋势以及面临的挑战等问题进行评述。

关键词: 代谢组学, 质谱, 毒理学, 临床化学

Abstract: Metabonomics is a science to study the kinds and amounts of metabolites and dynamic variation rule of the dynamic multiparametric metabolic response of living systems to pathophysiological stimuli or genetic variations, protein modification, the environment changes. Recently, metabonomics is mainly used in toxicology, disease diagnosis, traditional Chinese medicine and other fields. Referring to the recent literatures from both home and abroad, the latest advances in sample preparation, instrumental analysis techniques, data processing methods, as well as applications in current metabolomics studies are reviewed in the present paper.

Key words: metabolomics, mass spectrum, toxicology, clinical chemistry

王风萍, 郭春燕. 代谢组学及其研究新进展[J]. 神经药理学报, 2012, 2(6): 49-55.

WANG Feng-ping, GUO Chun-yan. Metabonomics and New Advances in Metabonomics[J]. ACTA NEUROPHARMACOLOGICA, 2012, 2(6): 49-55.

参考文献

[1] Stephen G Oliver, Michael K Winson, Douglas B Kell, et al. Systematic functional analysis of the yeast genome[J]. Trends Biotechnology, 1998, 16(9): 373-378.

[2] Stephen G Oliver. From gene to screen with yeast[J]. Curr Opin Genet Dev, 1997, 7(3): 405-409.

[3] Nicholson J K, Lindon J C, Holmes E. 'Metabonomics': understanding the metabolic responses of living systems to pathophysiological stimuli via multivariate statistical analysis of biological NMR spectroscopic data[J]. Xenobiotica, 1999, 29(11): 1181-1189.

[4] Aurelie Roux, Dominique Lison, Christophe Junot, et al. Applications of liquid chromatography coupled to mass spectrometry-based metabolomics in clinical chemistry and toxicology: A review[J]. Clinical Biochemistry, 2011, 44(1): 119-135.

[5] Janet Taylor, Ross D King, Thomas Altmann, et al. Application of metabolomics to plant genotype discrimination using statistics and machine learning[J]. Bioinformatics, 2002, 18(suppl 2): S241-S248.

[6] Holmes E, Nicholls A, Lindon J, et al. Development of a model for classification of toxin‐induced lesions using 1H NMR spectroscopy of urine combined with pattern recognition[J]. NMR in Biomedicine, 1998, 11(4-5): 235-244.

[7] Oliver Fiehn, Joachim Kopka, Richard N Trethewey, et al. Identification of uncommon plant metabolites based on calculation of elemental compositions using gas chromatography and quadrupole mass spectrometry[J]. Analytical Chemistry, 2000, 72(15): 3573-3580.

[8] Asaph Aharoni, Ric De Vos, Henricus Verhoeven, et al. Nontargeted metabolome analysis by use of Fourier transform ion cyclotron mass spectrometry[J]. OMICS, 2002, 6(3): 217-234.

[9] Sunia A Trauger, Eden P Go, Shen Zhou-xin, et al. High sensitivity and analyte capture with desorption/ionization mass spectrometry on silylated porous silicon[J]. Analytical Chemistry, 2004, 76(15): 4484-4489.

[10] Rebecca E Williams, Eva M Lenz, Julie A Evans, et al. A combined 1H NMR and HPLC–MS-based metabonomic study of urine from obese (fa/fa) Zucker and normal Wistar-derived rats[J]. J Pharm Biomed Anal, 2005, 38(3): 465-471.

[11] Katja Dettmer, Pavel A Aronov, Bruce D Hammock. Mass spectrometry-based metabolomics[J]. Mass Spectrom Rev, 2007, 26(1): 51-78.

[12] Huang Guang-ming, Chen Hao, Zhang Xin-rong, et al. Rapid screening of anabolic steroids in urine by reactive desorption electrospray ionization[J]. Analytical Chemistry, 2007, 79(21): 8327-8332.

[13] Jia L, Wang C, Zhao S, et al. Metabolomic identification of potential phospholipid biomarkers for chronic glomerulonephritis by using high performance liquid chromatography–mass spectrometry[J]. J Chromatography B, 2007, 860(1): 134-140.

[14] Jeremy K Nicholson, Higham D P, Timbrell J A, et al. Quantitative high resolution 1H NMR urinalysis studies on the biochemical effects of cadmium in the rat[J]. Molecular Pharmacology, 1989, 36(3): 398-404.

[15] Jeremy K Nicholson, John Connelly, John C Lindon, et al. Metabonomics: a platform for studying drug toxicity and gene function[J]. Nat Rev Drug Discov, 2002, 1(2): 153-161.

[16] Eva M Lenz, Bright J, Wilson I D, et al. A 1H NMR-based metabonomic study of urine and plasma samples obtained from healthy human subjects[J]. J Pharm Biomed Anal, 2003, 33(5): 1103-1115.

[17] John C Lindon, Jeremy K Nicholson. Spectroscopic and statistical techniques for information recovery in metabonomics and metabolomics[J]. Annu Rev Anal Chem, 2008, 1(1): 45-69.

[18] So-Young Park, Young-Woon Kim, Ji-Eun Kim, et al. Age-associated changes in fat metabolism in the rat and its relation to sympathetic activity[J]. Life Sciences, 2006, 79(23): 2228-2233.

[19] Mark P Hodson, Gordon Dear, Andy D Roberts, et al. A gender-specific discriminator in Sprague–Dawley rat urine: The deployment of a metabolic profiling strategy for biomarker discovery and identification[J]. Analytical Biochemistry, 2007, 362(2): 182-192.

[20] Robert Plumb, Jennifer Granger, Chris Stumpf, et al. Metabonomic analysis of mouse urine by liquid-chromatography-time of flight mass spectrometry (LC-TOFMS): detection of strain, diurnal and gender differences[J]. Analyst, 2003, 128(7): 819-823.

[21] Claire L Gavaghan, Elaine Holmes, Eva Lenz, et al. An NMR-based metabonomic approach to investigate the biochemical consequences of genetic strain differences: application to the C57BL10J and Alpk:ApfCD mouse[J]. FEBS Letters, 2000, 484(3): 169-174.

[22] Timothy M D Ebbels, Elaine Holmes, John C Lindon, et al. Evaluation of metabolic variation in normal rat strains from a statistical analysis of 1H NMR spectra of urine[J]. J Pharm Biomed Anal, 2004, 36(4): 823-833.

[23] Phipps A N, Stewart J, Wright B, et al. Effect of diet on the urinary excretion of hippuric acid and other dietary-derived aromatics in rat. A complex interaction between diet, gut microflora and substrate specificity[J]. Xenobiotica, 1998, 28(5): 527-537.

[24] Erik J Saude, Darryl Adamko, Brian H Rowe, et al. Variation of metabolites in normal human urine[J]. Metabolomics, 2007, 3(4): 439-451.

[25] Kay A Lawton, Alvin Berger, Matthew Mitchell, et al. Analysis of the adult human plasma metabolome[J]. Pharmacogenomics, 2008, 9(4): 383-397.

[26] Bathanne M Warrack, Serhiy Hnatyshyn, Karl-Heinz Ott, et al. Normalization strategies for metabonomic analysis of urine samples[J]. J Chromatography B, 2009, 877(5–6): 547-552.

[27] Christopher J Clarke, John N Haselden. Metabolic profiling as a tool for understanding mechanisms of toxicity[J]. Toxicologic Pathology, 2008, 36(1): 140-147.

[28] John C Lindon, Elaine Holmes, Jeremy K Nicholson. Metabonomics in pharmaceutical R & D[J]. FEBS J, 2007, 274(5): 1140-1151.

[29] Vincent Haufroid, Marek Jakubowski, Beata Janasik, et al. Interest of genotyping and phenotyping of drug-metabolizing enzymes for the interpretation of biological monitoring of exposure to styrene[J]. Pharmaco Genomics, 2002, 12(9): 691-702.

[30] Timothy W Gant. Novel and future applications of microarrays in toxicological research[J]. Expert Opinion on Drug Metabolism & Toxicology, 2007, 3(4): 599-608.

[31] Tomer K. A parallel approach to identifying biomarkers[J]. Environmental health perspectives, 2003, 111(11): A578.

[32] Timbrell J. Principles of biochemical toxicology[M]. CRC Press, 1999.

[33] Shockcor J P, Holmes E. Metabonomic applications in toxicity screening and disease diagnosis[J]. Current Topics Medicinal Chemistry, 2002, 2(1): 35-51.

[34] Julian L Griffin. Metabonomics: NMR spectroscopy and pattern recognition analysis of body fluids and tissues for characterisation of xenobiotic toxicity and disease diagnosis[J]. Curr Opin Chem Biol, 2003, 7(5): 648-654.

[35] John C Lindon, Jeremy K Nicholson, Elaine Holmes, et al. Contemporary issues in toxicology the role of metabonomics in toxicology and its evaluation by the COMET project[J]. Toxicology Applied Pharmacology, 2003, 187(3): 137-146.

[36] Donald G Robertson, Michael D Reily, J David Baker. Metabonomics in preclinical drug development[J]. Expert Opinion Drug Metab Toxicol, 2005, 1(3): 363-376.

[37] Hector C Keun. Metabonomic modeling of drug toxicity[J]. Pharmacology & therapeutics, 2006, 109(1): 92-106.

[38] Richard D Beger, Sun Jin-chun, Laura K Schnackenberg. Metabolomics approaches for discovering biomarkers of drug-induced hepatotoxicity and nephrotoxicity[J]. Toxicology Applied Pharmacology, 2010, 243(2): 154-166.

[39] Sun Jin-chun, Laura K Schnackenberg, Ricky D Holland, et al. Metabonomics evaluation of urine from rats given acute and chronic doses of acetaminophen using NMR and UPLC/MS[J]. J Chromatography B, 2008, 871(2): 328-340.

[40] Laura Schnackenberg, Chen Min-jun, Sun Jin-chun, et al. Evaluations of the trans-sulfuration pathway in multiple liver toxicity studies[J]. Toxicology Applied Pharmacology, 2009, 235(1): 25-32.

[41] Sookie La, Hye Hyun Yoo, Dong-Hyun Kim. Liquid chromatography-mass spectrometric analysis of urinary metabolites and their pattern recognition for the prediction of drug-induced hepatotoxicity[J]. Chemical Research Toxicology, 2005, 18(12): 1887-1896.

[42] Kurt J Boudonck, Matthew Mitchell, Laszlo Német, et al. Discovery of metabolomics biomarkers for early detection of nephrotoxicity[J]. Toxicologic Pathology, 2009, 37(3): 280-292.

[43] Erwin Van Vliet, Siegfried Morath, Chantra Eskes, et al. A novel in vitro metabolomics approach for neurotoxicity testing, proof of principle for methyl mercury chloride and caffeine[J]. Neurotoxicology, 2008, 29(1): 1-12.

[44] Donald H Chace. Mass spectrometry in the clinical laboratory[J]. Chem Rev, 2001, 101(2): 445-478.

[45] Matej Oreši?, Satu Simell, Marko Sysi-Aho, et al. Dysregulation of lipid and amino acid metabolism precedes islet autoimmunity in children who later progress to type 1 diabetes[J]. J Experimental Medicine, 2008, 205(13): 2975-2984.

[46] Shawn A Ritchie, Pearson W K Ahiahonu, Dushmanthi Jayasinghe, et al. Reduced levels of hydroxylated, polyunsaturated ultra long-chain fatty acids in the serum of colorectal cancer patients: implications for early screening and detection[J]. BMC medicine, 2010, 8(1): 13.

[47] 毛厌草, 单进军, 吴皓, 等. 代谢组学在中药及其复方领域中的研究进展[J]. 南京中医药大学学报, 2014, (02): 197-200.

[48] Lu Xiu-mei, Xiong Zhi-li, Li Jing-jing, et al. Metabonomic study on ‘Kidney-Yang Deficiency syndrome’ and intervention effects of Rhizoma Drynariae extracts in rats using ultra performance liquid chromatography coupled with mass spectrometry[J]. Talanta, 2011, 83(3): 700-708.

[49] Tong Xin, Sun Hui, Yan Guang-li, et al. Evaluation study on urine metabolomics in Yinhuang rat model induced by triplet factors of rhubarb, ethanol, and α-nephthylisothiolyanate[J]. Chin J Integr Med, 2011, 17(5): 369-375.

[50] Wang Shi-xiang, Luo Kai, Liang Jing, et al. Metabolomics study on the synergistic interaction between Salvia miltiorrhiza and Lignum dalbergiae odoriferae used as ‘Jun-Shi’ herbs in a S. miltiorrhiza recipe[J]. Medicinal Chemistry Research, 2011, 20(1): 16-22.

[51] 罗和古, 丁杰, 岳广欣, 等. 大鼠肝郁脾虚证的代谢组学研究[J]. 中西医结合学报, 2007, (03): 307-313.

[52] 徐舒, 陈合兵, 李洪, 等. “肝郁证”大鼠模型的建立及代谢组学的初步研究[J]. 中华中医药杂志, 2009, (06): 787-791.