益肾化浊法通过ngn1基因竞争性调控NSCs向神经元分化及其表观遗传学机制研究

项目名称： 益肾化浊法通过ngn1基因竞争性调控NSCs向神经元分化及其表观遗传学机制研究

项目编号： No.81202654

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 张琳琳

作者单位： 天津中医药大学

项目金额： 23万元

中文摘要： 阿尔兹海默病（Alzheimer's disease，AD）是一种中枢神经系统退行性疾病，其发病机制与大脑海马区神经元减少密切相关。Ngn1作为关键因子具有竞争性调控NSCs向神经元分化的作用。本课题组前期研究发现益肾化浊法可促进NSCs增殖并趋向神经元分化，基于此，本研究拟通过建立AD动物模型，以益肾化浊法中药干预，采用动物行为学、形态学与分子生物学检测，观察该法对NSCs向神经元分化的竞争性调控作用。通过细胞培养，采用siRNA技术进一步明析ngn1基因为该法产生竞争性调控的关键靶点；采用免疫共沉淀法观察ngn1基因相关组蛋白修饰的变化，揭示该法对ngn1基因产生靶向作用的表观遗传学机制。上述实验将从整体到微观逐步探讨益肾化浊法通过ngn1基因竞争性调控NSCs向神经元分化的靶向途径与发生机理，探索中医药防治AD的作用机制，发展中医"肾藏精"理论，为提升其临床应用价值提供部分实验依据。

中文关键词： 益肾化浊法；Neurogenin1；神经元分化；调控；表观遗传学

英文摘要： Alzheimer's disease (AD) is a kind of regressive disease of central nervous system（CNS）,its pathogenesis is closely ralated with the reduce of neurons in the hippocampus.NGn1, as a key factor, has competitive regulation effect on NSCs differenting into neurons.In previous studies we found that YSHZ method could promote NSCs proliferation and tend to differentiating into neurous.Based on this,this study intend to establish the animal model of AD,interventing with chinese herbs of YSHZ mothed,and observe competitive regulation effect of this mothod on NSCs differentiation by animal behavior、morphology and molecular biology detection.In cell experiments, we further clarify the key target- - ngn1 which this method effect on by siRNA technology. We observe ngn1 related histone modified changes by the methods of co-immunopre -cipitation, and revealed epigenetics mechanism of this method targeted to ngn1 gene.The above experiments will gradually explore the targeted way and effect mechanism of YSHZ method competitivly regulate NSCs differentiating into neurous through ngn1,from the whole to the micro.The purpose is to explore mechanism of chinese medicine prevention and therapy of AD,to develop the Chinese medicine theory "kidney hide fine" ,and provide the evidences for improving the clinical application value.

英文关键词： Yishen Huazhuo method；Neurogenin1；neuron；regulation；epigenetics