基于复杂体系信息获取和评价技术的中药分析方法学研究

项目名称： 基于复杂体系信息获取和评价技术的中药分析方法学研究

项目编号： No.30873196

项目类型： 面上项目

立项/批准年度： 2009

项目学科： 武器工业

项目作者： 柴逸峰

作者单位： 中国人民解放军第二军医大学

项目金额： 34万元

中文摘要： 本研究以方-证-效-化学组分群为核心，采用西医小鼠阿霉素心肌病模型、大鼠心肌梗死模型以及甲减脾肾阳虚模型作为中医证的表征，以代谢指纹谱的方法将成分和活性相结合，开展了基于气质联用、液质联用、核磁共振技术和细胞膜色谱等多种分析技术联合的中药四逆汤成分与药效的全面研究，建立了基于反相和亲水作用色谱相结合、核磁共振波谱和液质联用技术相结合、细胞膜色谱和二维色谱质谱联用技术相结合的多种中药分析的新方法和技术平台，筛选鉴定了四逆汤中潜在的活性成分，阐明四逆汤治疗阿霉素心肌、心肌梗死和甲减脾肾阳虚的作用机理，证明了四逆汤通过调节糖酵解、脂肪酸氧化、三羧酸循环、氨基酸代谢等代谢通路而调节机体能量代谢，发挥抗阿霉素心肌病的作用和治疗心肌梗死的作用；通过调节三羧酸循环、氨基酸代谢、鞘脂代谢等代谢通路而产生治疗甲减脾肾阳虚的作用。本项目的研究不仅为四逆汤的进一步开发提供科学依据，也为其它中药复方的药效作用和活性成分筛选提供了参考。项目研究发表论文17篇，其中SCI论文13篇，总影响因子达32分，培养研究生4名，超额完成任务指标。

中文关键词： 中药复杂体系；四逆汤；代谢组学；细胞膜色谱；心肌梗死

英文摘要： From the perspective of the relationship of prescription-syndrome-effect-chemical compositions, we combined the chemical compositions with bioactivities of Traditional Chinese medicine (TCM) based on the metabolic fingerprinting approach. By using cardiomyopathy mice models induced by doxorubicin, myocardial infarction (MI) rat models by left coronary artery ligation, and propylthiouracil-induced hypothyroidism models as profiles of TCM syndrome, we carried out the system and global studies of chemical components and bioactivities of Sini decoction (SND) based on multi-analytical techniques including gas chromatography-mass spectrometry, liquid chromatography-mass spectrometry (LC-MS), nuclear magnetic resonance (NMR) and cell membrane chromatography (CMC) technique. We established the new analytical method and analytical platform for TCM based on the combination of reversed-phase and hydrophilic interaction liquid chromatography, the combination of NMR and LC-MS, and combination of CMC and two dimensional LC-MS. We screened and identified the potential effective compounds of SND and explain the mechanism-of-action of SND effect on cardiomyopathy, MI and hypothyroidism. It was revealed that SND can regulate energy metabolism of cardiomyopathy and MI rat by intervening in glycolysis, lipid metabolism, citric acid cycle, and some amino acids metabolisms and then improve myocardial function. We also revealed that SND could play its role in propylthiouracil-induced hypothyroidism by intervening in citric acid cycle, amino acids metabolism and sphingolipid metabolism. The studies not only provided a basis for further research and development of SND and also provided a new methodological cue for studying the holistic efficacy and effective components of the other herbal formulae. By carrying out the project, we have published 17 papers including 13 SCI articles (total impact factor more than 31) and train 4 postgraduate students.

英文关键词： Complex system of Chinese medicine; Sini decoction; metabonomics; cell membrane chromatography; myocardial infarction