药物动力学与代谢组学对中药现代化研究的促进作用

近年来,随着药物动力学与代谢组学的深入发展,其对中药研究具有重要的理论指导意义和实践应用价值.该文综述了国内外药物动力学与代谢组学在阐明中药作用机制、给药方案、质量控制、新药开发和剂型改进、安全性与毒性评价、整体疗效与物质基础的关系、以及中药在体内的代谢指纹图谱研究等方面的具体应用,概述了两学科目前在中药研究中面临的挑...     

代谢组学技术的整合运用及其在中药现代化中的应用展望

代谢组学已经成为当今生物与医药领域的研究热点，作为系统生物学的核心组学，与其他组学进行的系统性研究为中药作用机制研究提供了思路和方法。质谱、核磁共振等现代分析技术作为代谢组学研究的技术平台，它们的整合运用加速了代谢组学的研究进程。本文就代谢组学技术的整合运用及研究现状作了简要的概述，并对代谢组学在中药现代化过程中的研究前景进行了展望。     

代谢物组学的研究进展

代谢物组学是继基因组学和蛋白质组学发展起来的一门新的组学(-omics)技术,是研究药物毒理和基因功能的技术平台,通过分析生物的体液、组织中的内源性代谢产物谱的变化来研究整体的生物学状况和基因调节功能.代谢物组学所涉及的主要技术为核磁共振技术和模式识别分析.对代谢物组学研究的样品、核心技术、分析方法和应用等几方面作简要概述.     

代谢组学及其在药学中的应用

目的对代谢组学(metabonomics)、代谢组学的主要研究方法和代谢组学在药学各领域中的应用作一综述。方法检索归纳相关文献35篇,按照代谢组学的基本思想、研究方法、在药学各领域的应用分类综述。结果代谢组学在药学领域中广泛应用于药物安全性评价、作用机制研究、新药的研发和中药的药效物质基础研究。     

Metabonomics in toxicology: a review.

Metabonomics and its many pseudonyms (metabolomics, metabolic profiling, etc.) have exploded onto the scientific scene in the past 2 to 3 years. Nowhere has the impact been more profound than within the toxicology community. Within this community there exists a great deal of uncertainty about whether metabonomics is something to count on or just the most recent technological flash in the pan. Much of the uncertainty is due to unfamiliarity with analytical and chemometric facets of the technology and the attendant fear of any "black-box." With those fears in mind, metabonomics technology is reviewed with particular emphasis on toxicologic applications in preclinical drug development. The jargon, logistics, and applications of the technology are covered in some detail with emphasis on recent work in the field.     

Magnetic resonance methods and applications in pharmaceutical research

This review presents an overview of some recent magnetic resonance (MR) techniques for pharmaceutical research. MR is noninvasive, and does not expose subjects to ionizing radiation. Some methods that have been used in pharmaceutical research MR include magnetic resonance spectroscopy (MRS) and magnetic resonance imaging (MRI) methods, among them, diffusion-weighted MRI, perfusion-weighted MRI, functional MRI, molecular imaging and contrast-enhance MRI. Some applications of MR in pharmaceutical research include MR in metabonomics, in vivo MRS, studies in cerebral ischemia and infarction, degenerative joint diseases, oncology, cardiovascular disorders, respiratory diseases and skin diseases. Some of these techniques, such as cardiac and joint imaging, or brain fMRI are standard, and are providing relevant data routinely. Skin MR and hyperpolarized gas lung MRI are still experimental. In conclusion, considering the importance of finding and characterizing biomarkers for improved drug evaluation, it can be expected that the use of MR techniques in pharmaceutical research is going to increase in the near future.     

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。     

代谢组学及其在药理学中的进展

随着化学检测技术和数据处理技术的发展,代谢组学成为了基因功能研究的重要手段,该文对代谢组学的基本知识和基本技术进行了介绍,对其在药理学研究中的应用作了综述和展望。     

Longitudinal pharmacometabonomics for predicting patient responses to therapy: drug metabolism, toxicity and efficacy

Pharmacometabonomics describes the use of metabolic profiling of biofluids, tissues and tissue extracts to predict, prior to dosing, the beneficial and adverse effects of an intervention such as drug administration. The approach not only is analogous to pharmacogenomics but also is sensitive to environmental factors such as the gut microbiome. Recent applications of pharmacometabonomics are presented and the extension to the use of longitudinal sampling is introduced. Clinical and other human applications of pharmacometabonomics are highlighted and possible future clinical applications of pharmacometabonomics and longitudinal pharmacometabonomics are discussed. These include clinical trials of new drugs either at the first-into-man stage or later in Phase II and III trials, and assessment of individual patients or groups of patients for particular therapies (personalised and stratified medicine approaches). Since metabonomics approaches are sensitive to both the host genome effects and the gut microbiome, pharmacometabonomics has particular utility for studying the host-microbiome interactions and for assessing new therapies that target the gut bacteria. Since the microbiome also has implications for nutrition and drug pharmacokinetics, such metabolic profiling approaches are likely to of use in such studies. It is anticipated that as metabonomics analytical and statistical technologies continue to develop, more applications will be realised and these should find use in real clinical situations, even monitoring patients in real time.     

代谢组学在肝肾损伤研究中的应用

代谢组学是近年来新发展起来的一门组学,已成为生物医学研究领域的新热点.由于其广泛的应用前景,目前已是系统生物学的重要组成部分.肝损伤及肾损伤是临床常见的危害人类健康的疾病,但目前的指标缺乏特异性,且灵敏度不高,造成临床上难以对肝肾损伤做出准确而及时的预警和监测.代谢组学能从代谢的角度整体分析疾病,快速、安全地对疾病的严重程度进行判别,在肝肾损伤的早期诊断等方面的研究已初显优势.本文主要综述了代谢组学技术在肝肾损伤研究中的应用现状.     

细胞代谢组学及其应用

细胞代谢组学通常被定义为胞内和细胞膜小分子代谢物的集合,而代谢物参与胞内进程的多种变化,其浓度可近似地反映一个器官、组织或细胞的表型。细胞代谢组学是一个新兴发展的领域,它可解决基本的生物学问题,并允许观察细胞内的代谢现象。在后基因时代,与当前其他常用的方法相比,细胞代谢组学具有许多潜在的优势,已成为一个有前途的分析工具。现简要综述细胞代谢组学的主要研究流程及其应用、与其他组学联用等方面的研究进展。     

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。     

代谢组学技术在痛风类疾病研究中的应用进展

目的 对近年来代谢组学技术在痛风领域的相关研究进行综述,以期为痛风今后更深入的研究提供思路和方向.方法 通过PubMed检索相关文献,分析和总结代谢组学技术在嘌呤代谢、高尿酸血症和痛风相关疾病研究中的应用.结果 代谢组学技术被广泛应用于痛风类疾病的生物标志物发现、发病机制探索以及药物作用机制研究,同时代谢组学技术与其他...     

Spectroscopic and statistical methods in metabonomics

Metabonomics is rapidly evolving through advances in analytical technologies together with the development of new hyphenated approaches that are increasingly being applied to analyze complex biological systems. Improvements in analytical performance, such as increased sensitivity and selectivity, are providing greater resolution to analytical datasets and the rich potential of metabonomics as a systems biology tool of choice is becoming clear. However, such improvements are resulting in datasets becoming increasingly demanding in terms of data handling and interpretation, and the degree to which metabonomics continues to develop will be dependent on how chemometrics and data-handling approaches keep pace with continually improving analytical technologies. This review provides an overview of the field of metabonomics, with a particular focus on the analytical techniques that are chiefly employed and the chemometric methods that have found most use. However, in addition, we mention less widely used analytical methods and suggest that advanced statistical methods will play a larger role in the future.     

代谢组学在关节炎中的研究进展

代谢组学是继蛋白质组学、转录组学、基因组学之后兴起的一门“组学”,它对体内生化反应的中间产物和终产物进行定性、定量分析,是对上述3种组学的延伸。本文介绍了代谢组学的主流分析平台及其在关节炎模型中的应用,并就中西药对关节炎治疗作用的代谢组学以及与之相关的生物标志物作一综述。     

Application of metabonomics in drug development

Metabolic profiling (metabonomics/metabolomics) is the untargeted analysis of metabolic composition in a biological sample, and is principally aimed at biomarker discovery. The frequent use of noninvasive biofluid analysis in metabonomics is suited to the clinic and facilitates dynamic monitoring. Analytical protocols for metabolic biomarkers are potentially robust because a metabolite is the same chemical entity irrespective of its origin, facilitating 'bench-to-bedside' translational research. Metabonomics can make an impact at several points in the drug-development process: target identification; lead discovery and optimization; preclinical efficacy and safety assessment; mode-of-action and mechanistic toxicology; patient stratification; and clinical pharmacological monitoring. This review describes and exemplifies the latest developments in each of these areas, including the impact of new data and chemical analytical techniques. The future goals for metabonomics are the validation of existing biomarkers, in terms of mechanism and translation to man, together with a focus on characterizing the individual ('personalized healthcare').     

Application of high-throughput Fourier-transform infrared spectroscopy in toxicology studies: contribution to a study on the development of an animal model for idiosyncratic toxicity

An evaluation of high-throughput Fourier-transform infrared spectroscopy (FT-IR) as a technology that could support a "metabonomics" component in toxicological studies of drug candidates is presented. The hypothesis tested in this study was that FT-IR had sufficient resolving power to discriminate between urine collected from control rat populations and rats subjected to treatment with a potent inflammatory agent, bacterial lipopolysaccharide (LPS). It was also hypothesized that co-administration of LPS with ranitidine, a drug associated with reports of idiosyncratic susceptibility, would induce hepatotoxicity in rats and that this could be detected non-invasively by an FT-IR-based metabonomics approach. The co-administration of LPS with "idiosyncratic" drugs represents an attempt to develop a predictive model of idiosyncratic toxicity and FT-IR is used herein to support characterization of this model. FT-IR spectra are high dimensional and the use of genetic programming to identify spectral sub-regions that most contribute to discrimination is demonstrated. FT-IR is rapid, reagentless, highly reproducible and inexpensive. Results from this pilot study indicate it could be extended to routine applications in toxicology and to supporting characterization of a new animal model for idiosyncratic susceptibility.     

整合代谢组学和生物信息学策略在解析中药系统复杂性中的应用

中药在化学组成方面的复杂性决定了其作用方式和作用过程的复杂性。传统研究方法缺乏系统性,使得一系列制约中药现代化发展的关键问题一直未能得到很好的解决,包括中药化学物质组表征、中药作用机制、中药方剂配伍规律以及中药毒性机制等中药系统复杂性问题。代谢组学作为一门全新的组学技术,秉承了从机体全局系统出发来考量机体内源性小分子物质与外源性干预物质（如药物）的相互作用的理念,与在中医药理论指导下的中药作用原理思路一致。近年来,人们尝试将整合代谢组学技术和生物信息学策略用于解开上述中药关键问题,并已取得了一定的成果。但其在理论挖掘、策略设计、方法开发和实践拓展诸多方面都有很多具体的工作需要进一步推进。对整合代谢组学和生物信息学策略在解析中药系统复杂性中的应用进行综述。     

代谢组学的发展与药物研究开发

代谢组学是近年来新发展起来的一门组学,其主要研究体系有生物体液、生物组织及单个细胞的代谢组,利用一些现代的分析技术,如NMR、LC-MS、GC-MS等,取得整个研究体系的多维数据后,利用模式识别和专家系统技术寻找其中的系统生物学信息。本文从代谢组学的发展,代谢组学的研究范围和研究方法,以及在药物的作用机制和安全性评价,疾病模型,特别是中药研究的应用等方面予以阐述。