补肾生髓法通过NF及NRG1调节轴突髓鞘化作用机制的研究

项目名称： 补肾生髓法通过NF及NRG1调节轴突髓鞘化作用机制的研究

项目编号： No.81473640

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： 樊永平

作者单位： 首都医科大学

项目金额： 75万元

中文摘要： 神经丝(NF)、神经调节素-1(NRG1)分别是构成轴突的主要结构和轴突膜表面的信号转导分子，在促进轴突髓鞘化即多发性硬化(MS)神经功能损伤修复具有重要作用。本研究以补肾生髓为基础理论，经前期临床疗效观察奠定了以生熟地、制首乌为补肾生髓基础方药。通过对其主要活性物质梓醇/大黄素的提取，探讨梓醇/大黄素通过NF及NRG1促进轴突髓鞘化的机制。本研究利用动物实验和神经元与少突胶质细胞前体细胞(OPC)共培养技术，观察梓醇/大黄素对轴突与髓鞘在体与离体的影响。通过不同剂量的梓醇/大黄素干预，使用多种检测方法，从基因、蛋白、组织水平观察轴突与髓鞘Olig1，Olig2，NRG1 ，NF200，MBP等多项指标的表达。综合病理观察及各项指标的变化，探讨梓醇/大黄素对神经元轴突保护及自身髓鞘化作用机制，为补肾生髓促进MS髓鞘修复提供科学依据.

中文关键词： 中药复方；实验研究；信号通路

英文摘要： Neurofilament (NF) and neuregulin-1(NRG1) are the main structure of axon and signal transduction molecule in axonal membrane respectively. They play a significant role in promoting myelination and neurological damage repair from multiple sclerosis( MS). This study based on the theory of Tonifying the kidney and establish Rehmannia and Radix as basis prescriptions of Tonifying the kidney by laying a pre-clinical efficacy. By extracting their main active substances catalpol / emodin, we explore the role of myelination of catalpol / emodin by NF and NRG1. Using animal experiments and co-culture of neuron and oligodendrocytes precursor cell (OPC) technique, we observe the effect of catalpol / emodin to NF and NRG1 in vitro and in vivo.Through different doses of catalpol / emodin intervention, using a variety of methods detect the expression of axons and myelin Olig1, Olig2, NRG1, NF200, MBP observations from a number of indicators, such as genes, proteins, tissue levels. These experiments will explore the impact of catalpol / emodin in myelination, elaborate the mechanism of catalpol / emodin in myelination through NF and NRG1 from the tissue, cellular and molecular level and offer experimental data and scientific basis for Tonifying the kidney in treating MS.

英文关键词： Chinese herbal compound;Experimental Study;Signaling pathway