基于SELEX方法的研究栀子苷及其与三七总皂苷配伍防治AD的多靶点协同作用机制

项目名称： 基于SELEX方法的研究栀子苷及其与三七总皂苷配伍防治AD的多靶点协同作用机制

项目编号： No.81473546

项目类型： 面上项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 华茜

作者单位： 北京中医药大学

项目金额： 72万元

中文摘要： 中药药效成分多为小分子物质，其分子靶钓及多靶点协同机制研究，缺乏高效特异性结合的配体。指数富集适体系统进化技术(SELEX)，是一种从DNA随机文库中筛选特异结合小分子物质的核酸适体技术，获得2009年诺贝尔生理医或医学奖。核酸适体是一种高效化学抗体，结合免疫磁珠技术有望用于中药药效物质的分子靶钓研究。栀子苷具有多种药理活性，我们在前期研究中发现栀子苷和三七总皂苷配伍可以促进三种阿尔茨海默症（AD）模型小鼠智能行为的改善，栀子苷对于三七总皂苷减少模型动物脑内毒性病理产物的产生及促进神经元形态可塑性都具有协同作用，但其协同作用的机制不清。本项目拟运用SELEX筛选栀子苷特异核酸适体，并在原代神经元和AD模型动物中进行栀子苷的分子靶钓，旨在运用核酸适体进行栀子苷与三七总皂苷配伍防治AD的多靶点协同机制研究；进一步地，以栀子苷为模型，建立中药小分子物质特异性核苷酸适体筛选的SELEX技术。

中文关键词： 分子靶钓；核酸适体；SELEX；协同机制；栀子苷

英文摘要： The medical effect ingredients are mostly small molecules in Chinese medicine. However, it is a lack of high specificity of aptamer to study their purification, target points in vivo and the mechanisms. Systematic evolution of ligands by exponential enrichment (SELEX) is a single stranded oligonucleotides technique of screening specific form from DNA random library, which won the 2009 Nobel physiological medicine or medicine prize. Nucleotide aptamer is a high efficient chemical antibody, which could be carried out research on molecular target of Chinese medicine accompanied with Immunomagnetic beads separation technique. Geniposide has a variety of pharmacological activities, such as anti-inflammatory, antioxidant, neuroprotection. In our previous study, we found that geniposide accompanied with Panax Notoginseng Saponins(PNS) could promote memory and behaviors in Alzheimer disease (AD) mice model. In addition, geniposide plays a synergistic effect on the production of endotoxic pathological products and synaptic plasticity. However, this synergistic effect remains unknown. To address this issue, we will use SELEX to screen the specific aptamer of geniposide both in primary neurons and AD mice model, to reveal the molecular mechanisms and its synergistic effect. Furthermore, based on this geniposide study, we try to establish SELEX technology in screening specific nucleotide aptamer of Chinese medicine.

英文关键词： Geniposide;molecular target;nucleotide aptamer;SELEX;synergistic effect