远志-石菖蒲干预注意缺陷多动障碍模型动物的代谢组学研究

项目名称： 远志-石菖蒲干预注意缺陷多动障碍模型动物的代谢组学研究

项目编号： No.81503616

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 倪新强

作者单位： 深圳大学

项目金额： 18万元

中文摘要： 中医药对其优势病种注意缺陷多动障碍（ADHD）的研究目前偏于多巴胺等神经递质代谢系统的药物干预；而ADHD更多生物标记物的发现、常规西药多靶点效应的明确、开发天然药物的迫切需要，提出了新的科学问题：中药的整体效应是否仍占优势？如何被科学解读？如何进一步构建ADHD中药筛选体系？我们前期发现远志－石菖蒲为临床ADHD常用药对；因此，本项目拟：1）采用动物行为学与代谢组学，递进式研究ADHD模型鼠在远志－石菖蒲治疗前后尿液、血液、脑组织及脑脊液“代谢物指纹图谱”的变化及其与药效学的关联；2）研究原代SHR大鼠纹状体与前额叶皮质神经元在远志－石菖蒲干预前后细胞水平的代谢组学；3）进一步构建表达多巴胺转运体(DAT)的HEK293细胞与CHO细胞，观察远志－石菖蒲对DAT在细胞水平的影响。本课题旨在为ADHD有效防治提供新理论与药物新靶点，进而寻找ADHD潜在的生物标记物及判断疗效的可靠预测指标。

中文关键词： 注意缺陷多动障碍；代谢组学；机制研究；远志－石菖蒲；动物实验

英文摘要： The study of Traditional Chinese medicine(TCM) on Attention deficit hyperactivity disorder (ADHD) are still focusing on the expression of the dopamine and other neurotransmitter by TCM treatment; but founding of the more biomarkers of ADHD, specification of multiple target of routine durgs, and the need of developing natural drug, has offered some new scientific questions: Is the overall efficacy of TCM still take the advantage over routine medicine? And how will it be interpreted scientificly? And how to make the TCM screening system for ADHD? our former study found the polygala tenuifolia-Rhizoma acori graminei is the most herbal pair for ADHD. This study is to study the change of metabolic fingerprint of urine, blood, cerebrospinal fluid and brain of ADHD model rats before and after the treatment of using the animal behavior testing and metabonomics; and study the change of metabolic fingerprint of nerve cell of corpus striatum and prefrontal cortex of SHR rats before and after the treatment of polygala tenuifolia-Rhizoma acori graminei; and further culture the HEK293 cell and CHO cell transfected with human dopamine transporter (DAT), and study the efficacy of polygala tenuifolia-Rhizoma acori graminei on the classic drug target of ADHD. This study is to offer the new theory and drug treatment target, and then look for the potential biomarkers and the valid predictive index, and boost the efficacy and scientificity of TCM in the treatment of ADHD.

英文关键词： Attention Deficit Hyperactiviey Disorder;Metabonomics;Mechanism study ;Polygala tenuifolia- Rhizoma acori graminei ;Animal study