基于代谢组学技术探讨高尿酸血症合并慢性肾脏疾病的研究进展

摘要：代谢组学具有灵敏、快速、高通量的特点,在研究内源性小分子的变化规律、发现异常代谢物、揭示个体代谢表征等方面具有应用潜力。利用代谢组学研究高尿酸血症合并慢性肾脏疾病是近年来的热点。对高尿酸血症合并慢性肾脏疾病的相关代谢组学的研究表明,该病与氨基酸、脂质代谢紊乱密切相关。就代谢组学在高尿酸血症合并慢性肾脏疾病发病机制探索、生物标志物筛选、中药治疗方面的应用展开综述。     

基于代谢组学的中药药效评价、药效物质发现及作用机制研究进展

中药药效物质及作用机制等中药有效性相关问题的科学阐释是解决制约中药现代化发展的有效途径。代谢组学与中医药的整体观、辨证论治特征相契合,以其高通量、整体性的研究特性高效解析中药整体药效作用过程。将中医药理论与代谢组学技术有机融合,可为深层次阐明中药的有效性、物质基础、作用机制等科学问题提供关键技术。综述了代谢组学方法解决中药药效评价与药效物质研究的具体实践,并对代谢组学策略的未来发展方向进行展望。     

代谢组学在中药研究和抗肿瘤研究中的应用进展

［摘要］代谢组学是近年来快速发展的“组学”,是代谢控制论提升的学科,是评价细胞和体液的内源性和外源代谢物浓度与功能关系的学科。代谢组学是后基因时代的一门新兴的独立学科。该学科的应用跨越生物技术和医药技术,具有广阔发展前景。代谢组学与药物药效和毒性筛选及评价研究和安全性评价、作用机制研究与合理治疗用药密切相关。从代谢组学技术用于中药研究的可行性、代谢组学的整体观念与中药作用的整体观念的一致性、代谢组学应用于恶性肿瘤的研究等3个方面阐述代谢组学与中药研究及抗肿瘤研究的关系,为代谢组学在中药研究和恶性肿瘤诊断方面的应用及其机制研究提供新的研究方法和思路。     

代谢组学技术在疾病诊断中的应用

代谢组学是一门在新陈代谢的动态进程中,系统研究代谢产物的变化规律,揭示机体生命活动代谢本质的科学。本文对代谢组学的概念、特点、研究方向及研究方法作了简要介绍,综述了当前代谢组学技术在临床疾病诊断中的应用,并对代谢组学的发展作了展望。     

代谢组学技术在糖尿病中的应用研究进展

摘要：近年来随着糖尿病患病率的增高,糖尿病对全球公共卫生事业及人类健康带来了严重的负担。糖尿病作为一种典型且复杂的代谢性疾病,代谢组学技术的特点使得其在糖尿病研究中起着不可忽视的重要作用,并取得重要的研究成果。本文将对代谢组学技术相关工具的发展和代谢组学应用,特别是代谢组学在妊娠糖尿病、2型糖尿病和糖尿病肾病的防治以及中药治疗糖尿病的应用研究进行总结和归纳,以期促进代谢组学技术在糖尿病中的应用。     

代谢组学在中药安全性评价中的应用

代谢组学是后基因时代的一种全新的组学技术,近年来发展极为迅速。随着基于核磁共振、质谱以及化学计量学软件的代谢组学分析技术平台的不断发展,代谢组学技术为中药毒性和安全性研究提供了崭新的和强有力的技术手段,并得到了广泛应用,如发现毒性物质、探讨毒性机制等。综述中药毒性及安全性评价领域代谢组学研究进展,并探讨其应用前景和存在的问题。     

代谢组学分析技术及代谢物鉴定

近年来,代谢组学技术在众多科学领域得到了广泛的应用。代谢组学研究的关键在于对大量小分子代谢产物进行快速、准确的分析鉴定,这在很大程度上依赖于相关技术的进步。磁共振、质谱、色谱以及毛细管电泳等技术的发展和联用,使得代谢组学的广泛应用成为可能。磁共振和质谱是代谢组学研究中最重要的两个技术平台,对代谢产物进行明确的鉴定是代谢组学研究的根本任务。本文就代谢组学相关分析技术及代谢物鉴定的研究进展作一综述。     

微阵列技术的进展

基因组学和转录组学的研究，促进了高通量药物筛选的发展。目前，高通量药物发现已经转向关注蛋白质组学、糖原组学和代谢组学评价中存在的难题。微阵列技术是评价基因表达的主要工具，它们也被用于蛋白质和小分子筛选库。微阵列技术能帮助人们从更小体积的样品中获得更多的信息，使得低花费的高通量分析在药物发现过程中成为可能。蛋白质组学、糖原组学和组织阵列技术的发展将进一步帮助和促进药物发现过程的实现。     

代谢组学的研究现状与展望

代谢组学是20世纪90年代中期发展起来的对某一生物或细胞所有低相对分子质量代谢产物进行定性和定量分析的一门新学科,由于其广泛的应用前景,目前已成为系统生物学的重要组成部分。现简要介绍了代谢组学的含义、代谢组学研究的历史沿革、当前代谢组学研究中的分析技术、数据解析方法,综述了代谢组学在药物毒理学研究、疾病诊断、植物和中药等领域的应用情况,并对当前代谢组学研究中存在的问题及发展趋势进行探讨。     

基于代谢组学技术的中药复方药效物质基础与作用机制研究

中药复方作为中医临床用药最广泛的形式,其药效物质基础和作用机制的科学阐释成为全面揭示中医药实用价值进而实现中药现代化的关键。代谢组学技术始于20世纪90年代中期,旨在利用现代科学技术研究生物体系在受到刺激或干扰后,内源性代谢物组的变化或随时间的变化规律,以代谢物组分析为基础,借助高通量检测和多元化数据处理手段,整合多维生物信息系统,阐明中药复方的药效物质基础和作用机制。综述了最新代谢组学技术的研究进展及在中药复方药效物质基础和作用机制研究中的应用情况,并对代谢组学技术未来发展趋势进行展望。     

Metabolomics in research of phytotherapeutics

Pharmaceutical and food industries are increasingly focused on the great potential of plant secondary metabolites or natural substances which can be used as therapeutics or model compounds for development of new drugs. The paper is devoted to the use of metabolomics, metabolic profiling and metabolic "fingerprint" for the identification of individual active phyto-substances in plant extracts, in profiling of unique groups of plant secondary metabolites that can be used to improve the classification of several species of medicinal plants as well as for a better characterization and quality control of medicinal extracts, tinctures and phytotherapeutic products prepared from these plants. Combined analytical methods and multivariate statistical analysis are used for metabolite identification. Using this approach, medicinal plants are evaluated not only on the basis of a limited number of pharmacologically important metabolites but also based on the fingerprints of minor metabolites and bioactive molecules.     

植物代谢组学技术在中药资源研究中的应用

植物代谢组学技术是借助多种检测手段以植物提取物中代谢物为研究对象进行全面定性、定量分析,继基因组学和蛋白质组学之后发展起来的一门新兴学科。随着核磁共振（NMR）、液相色谱-质谱联用（LC-MS）、气相色谱-质谱联用（GC-MS）等技术的快速发展,植物代谢组学已广泛应用于中药资源研究中。对该技术在中药基原鉴别、野生与栽培品的鉴别、药用部位鉴别、不同发育期的成分鉴定及不同产地药材的品质差异等方面研究进展进行综述,从而揭示植物代谢物动态变化趋势,为中药质量评价奠定基础。     

光调控对药用植物次生代谢成分合成的影响

药用植物次生代谢成分,因具有特殊的药理活性或功效对人类的健康极为重要,是药品、保健品、化妆品的主要来源。随着人类对于健康和长寿的不断追求,医药市场的需求规模持续增长,提高药用植物次生代谢成分的产量和质量变得特别重要。植物次生代谢成分是植物对环境的一种适应,是在长期进化过程中植物与生物和非生物因素相互作用的结果。药用植物次生代谢成分的产生和积累主要受植物遗传因素和环境因素的影响,其中光环境对其合成影响尤为重要,因而,长期以来光调控一直是国内外众多学者研究的热点。本文综述近年来有关光调控对药用植物次生代谢成分影响的研究进展,主要从光质、光强、光周期的影响分别阐述,以期为高效生产具有重要药理活性的次生代谢成分提供理论依据和实践指导。     

Mass spectrometry-based technologies for high-throughput metabolomics

The metabolome is composed of a vast number of small-molecule metabolites that exhibit a diversity of physical and chemical properties and exist over a wide dynamic range in biological samples. Multiple analytical techniques, used in a complementary manner, are required to achieve high coverage of the metabolome. MS is playing a central role in metabolomics research. Herein, we present a brief overview of the MS-based technologies employed for high-throughput metabolomics. These technologies range from chromatography-MS techniques, such as GC-MS and LC-MS, to chromatography-free techniques, such as direct infusion, matrix-assisted and matrix-free laser desorption/ionization, imaging and some new ambient ionization approaches. Chemoinformatics and bioinformatics tools are widely available to facilitate successful metabolomics studies by turning the complex metabolomics data into biological information through streamlined data processing, analysis and interpretation.     

Pharmacognosy and reverse pharmacognosy: a new concept for accelerating natural drug discovery

Combinatorial chemistry and high-throughput screening (HTS) have led to the identification of numerous agents that are active and selective in vitro. Identifying drugs that are active in vivo, however, remains a challenge. Traditional medicinal cures based on natural materials have proven useful for many populations worldwide, representing huge and disperse tracts of knowledge that are sometimes neglected in Western research due to differences in the concepts of illness. In this review we introduce a new approach, termed 'reverse pharmacognosy' (from diverse molecules to plants), which can be coupled with pharmacognosy (from biodiverse plants to molecules). Reverse pharmacognosy utilizes new techniques, such as HTS, virtual screening and a knowledge database containing the traditional uses of plants. Integrating pharmacognosy and reverse pharmacognosy in the research process may provide an efficient and rapid tool for natural drug discovery.     

Plants of Indian origin in drug discovery

The Indian system of medicine (ISM) consists of several major components such as Ayurveda, Siddha, Unani and homeopathy. All these components provide the major healthcare for a large part of the population in India and have been flourishing in this country for many centuries. Medicinal plants constitute a major part in all of these traditional systems. Several regulations and controls on the use of medicinal plants in traditional medicine have evolved. On the one hand, such regulations will help to cure different aliments through Indian indigenous resources and, on the other hand, they will help in the screening and evaluation of natural resources through the development of potential lead components in order to provide better healthcare through ISM. Several lead molecules have been developed from ISM. This review aims at highlighting aspects of drug development from Indian medicinal plants through the use of ethnobotany, ethnopharmacology and systems biology, with different approaches using metabolomics and allied fields.     

Mass spectrometry-based quantitative analysis and biomarker discovery

Mass spectrometry-based quantitative analysis and biomarker discovery using metabolomics approach represent one of the major platforms in clinical fields including for the prognosis or diagnosis, assessment of severity and response to therapy in a number of clinical disease states as well as therapeutic drug monitoring (TDM). This review first summarizes our mass spectrometry-based research strategy and some results on relationship between cysteinyl leukotriene (cysLT), thromboxane (TX), 12-hydroxyeicosatetraenoic acid (12-HETE) and other metabolites of arachidonic acid and diseases such as atopic dermatitis, rheumatoid arthritis and diabetes mellitus. For the purpose of evaluating the role of these metabolites of arachidonic acid in disease status, we have developed sensitive determination methods with simple solid-phase extraction and applied in clinical settings. In addition to these endogenous compounds, using mass spectrometry, we have developed actually applicable quantitative methods for TDM. Representative example was a method of TDM for sirolimus, one of the immunosuppressant agents for a recipient of organ transplant, which requires rigorous monitoring of blood level. As we recognized great potential in mass spectrometry during these researches, we have become interested in metabolomics as the non-targeted analysis of metabolites. Now, established strategy for the metabolomics investigation applies to samples from cells, animals and humans to separate groups based on altered patterns of metabolites in biological fluids and to identify metabolites as potential biomarkers discriminating groups. We would be honored if our research using mass spectrometry would contribute to provide useful information in the field of medical pharmacy.     

糖尿病并发症的靶向代谢组学研究进展

靶向代谢组学是代谢组学的重要组成部分,对目标明确的代谢产物在样本中的含量进行检测,具有特异性强、检测灵敏度高和定量准确等特点。应用靶向代谢组学研究疾病发生发展过程中的差异代谢物并阐明其代谢异常的机制,对疾病诊断及治疗具有重要意义。将靶向代谢组学在糖尿病周围神经病变、糖尿病视网膜病变、糖尿病肾病、糖尿病性认知功能障碍、糖尿病性心肌病及糖尿病性黄斑水肿中的应用进行归纳,整合不同疾病发生发展涉及的氨基酸代谢、脂代谢、三羧酸循环及糖酵解等多种代谢途径及相关的差异代谢物,整理了不同并发症的部分生物标志物,以期为后续深入研究、寻找疾病治疗新途径提供思路和方法。