中文摘要
中医药治疗阿尔兹海默病(AD)具有独特优势,从中药中研究有效防治AD的药物具有重要意义。本课题以中药红景天为研究对象,探索建立基于高分辨质谱和质谱成像技术的红景天治疗AD的药效物质基础和作用机制研究。利用HPLC-FT-ICR MS和HPLC-Q-TOF MS技术表征红景天体内外化学成分,建立红景天治疗AD的体外-入血-入脑脊液-入脑组织成分系列指纹谱;利用代谢组学技术建立并分析体液代谢谱的变化,找寻潜在的生物标志物;重点利用质谱成像技术可视化地开展红景天药效物质和内源性代谢物在大鼠脑组织的原位成像研究,建立药效物质和代谢物组之间的联系。本研究将从中医学整体观出发,通过体内与体外研究相结合、体内效应成分与内源性代谢物研究相结合、代谢组学与病理生理相结合的方法,综合评价红景天治疗AD的药效,明确其药效物质基础,阐释其作用机制,探索以创新性、整体性、高效性和系统性为特点的中药研究新思路。
英文摘要
In view of the unique advantages of traditional Chinese medicines(TCM) in the treatment of Alzheimer's disease(AD), it is significant for prevention and control of AD to research on TCM. In this project, Rhodiola was selected as the object and it will be studied based on the strategy by combining chemomics with metabonomics, and new methods based on high resolution mass spectrometry and imaging mass spectrometry(IMS) will be developed. Among them, a new method using HPLC-FT-ICR MS or HPLC-Q-TOF MS technology will be applied to separation and identification of chemical compounds from Rhodiola, and the chemical fingerprint in vitro and in vivo will be established respectively. Then,the metabonomics studies of Rhodiola will be carried out and the biomarkers related with the action mechanism will be found through analyzing the feature changes of the established ‘metabolic profiles’ of body fluids.And furthermore, a brand new method based on IMS will be explored for direct and simultaneous analysis of exogenous and endogenous compounds in rat tissue sections. In a word, embarking on concept of the wholism for TCM theories, the therapeutic basis and action mechanism of Rhodiola on AD will be illustrated by means of the combinations of in vivo and in vitro study, active ingredients and endogenous metabolites, metabolomics data and pathological physiology along with biochemistry indexes. In a word, a theoretical support for the clinical application of Rhodiola will be provided and a new way with innovativeness, holism, efficiency and systematicness aiming at TCM will be explored by this research.
