基于原位质谱成像技术研究人参和西洋参药性与神经调控的性-效关联

Study on the material basis and effect of Chinese medicine property is the key of traditional Chinese medicine research. Especially the composition characteristic and efficacy regularity of relative Chinese medicine property is the bottleneck of traditional Chinese medicine modernization research. According to previous research, the relevance of chemical components and property were presented under certain levels of composition and biological effect ranges. This project is focus on the properties of Panax species representative relatives, Ginseng and American Ginseng. According to the warm and cool property differences of these two similar Chinese medicine, the chemical composition and difference of them will be analyzed by ambient ionization mass spectrometry imaging (AIMSI) rapidly and directly. With the employment of chemometrics techniques, the characteristic components and composition relationship associated with property will be screened out. On that basis, by AIMSI characterization deeper into different brain regions, the existence form, spatial distribution and micro-area quantitation were studied. And the metabolisms of neurochemicals are summarized, and then the relation of nervous system regulatory effect and characteristic chemical components are discussed. By the systemic integrated analysis of correlation of property and characteristic components and correlation of nervous system regulatory effect and characteristic components, the correlation rule of warm and cool property and nervous system regulatory effect of Ginseng and American Ginseng will be clarified. This research will provide a methodology reference for the study of the material basis and pharmacological action of the relative Chinese medicine property difference.

中药药性物质基础及生物效应本质，是中药研究的关键科学问题，特别是亲缘相近中药药性成分特征和功效作用规律研究是传统中药现代化研究的瓶颈问题。前期研究工作表明，中药成分在一定构成上与药性在一定生物效应表达范围内存在关联性。本课题以人参属典型亲缘相近中药人参和西洋参的药性为切入点，从二者整体药性温凉差异程度出发，利用原位电离质谱成像技术，快速直接分析二者化学成分组成差异；结合化学计量学，筛选出与药性相关的特征组分及其组合关系。在此基础上，通过原位质谱成像表征，深入大鼠不同脑区，明确神经化学成分的存在形式、空间分布和微区定量，分析代谢规律，阐明人参和西洋参神经系统调控作用与特征组分之间的内在联系。将药性-特征组分相关性研究结果与神经系统调控作用-特征组分相关性研究结果系统整合，进而阐明人参和西洋参温凉药性与神经系统调控效应的关联规律，为亲缘相近中药药性差异的物质基础和药理作用研究提供方法学借鉴。

中药药性成分特征和功效作用规律研究是传统中药现代化研究的重点。本项目通过原位质谱成像技术结合代谢组学方法，研究中药药性物质基础及生物效应本质的基础科学问题。本项目以亲缘相近中药人参和西洋参对药性为切入点，筛选脑组织中与药性相关的特征神经化学物质25个，温性药性相关特征神经化学物质17个和凉性药性相关特征神经化学物质8个，建立判定药性特征程度的研究方法。筛选出人参和西洋参药性温凉差异的特征皂苷组分19个，其中温性药性相关特征皂苷15个和凉性药性相关特征标记物4个。以识别模型的判别系数作为药性相关特征标记，获得皂苷组分组合关系与药性程度的影响及其组合关系，原人参二醇型人参皂苷PPD总和与原人参二醇型人参皂苷PPT总和的比值大于2.5指示凉性药性，原人参二醇型人参皂苷PPD总和与原人参二醇型人参皂苷PPT总和的比值小于1.5指示温性药性。温性药性标记物具有促进机体能量代谢，改进机体内分泌系统功能，提高中枢神经系统兴奋性等生物活性，确定了温热药能够调理寒凉证。识别出的凉性药性标记物都具有降低中枢神经系统兴奋性作用，减弱代谢和应激反应能力，从而显示寒凉的生物活性。建立了人参和西洋参化学组分与神经系统调控作用相关性，阐明了温凉药性与神经系统调控效应的关联规律与差异，为亲缘相近中药药性差异的物质基础和药理作用研究提供方法学借鉴和新的研究思路。对中药药性的现代研究具有重要的学术意义和借鉴作用。本项目共发表学术论文3篇，其中SCI论文2篇（影响因子及分区5.195Q1/1.193Q4），科技核心论文1篇；获得软件著作权1项，申请发明专利1项；培养硕士研究生1名，已取得硕士学位。项目获拨直接经费20万元，支出18.4298万元，各项支出均与预算相符。剩余经费1.5702万元，剩余经费计划用于本项目研究后续支出。