基于血脑屏障模型过滤分析的兴安升麻抗AD神经炎症抑制剂的发现和构效关系研究

神经炎症是近年来备受关注的阿尔茨海默病（AD）发病学说，是AD发生和发展的重要影响因素之一。以神经炎症为切入点，寻找有效的AD治疗药物具有重要的意义和光明的前景。我们在前期工作中发现兴安升麻提取分离部位对Aβ侧脑室注射致小鼠学习记忆损伤具有显著的改善作用，但药效物质不明。本项目拟在此基础上，建立MDCK-MDR1血脑屏障细胞渗透性模型，对该活性部位进行过滤分析，应用LC-Q-TOF-MS方法对透膜成分进行快速甄别和检识，靶向分离并鉴定它们的结构，研究其抑制神经炎症的活性和构效关系，为发现活性更高、特异性更强的抗AD神经炎症抑制剂提供新的思路、方法和理论依据。

Neuroinflammation hypothesis, one of the most important factors during AD onset and progression, has been attracting considerable attention in recent years. Therefore, taking neuroinflammation as breakthrough point, exploring effective anti-neuroinflammatory agents for AD therapies is of very important significance. Our previous work found that the fraction of Cimicifuga dahurica (CD) had a remarkable improvement on the impairment of memory of Aβ-induced AD mice. Based on these research results, the blood-brain barrier (BBB) permeation model will be established by using MDCK-MDR1 cell lines to filter/screen the CD active fraction; afterwards, the rapid analysis and identification of permeable components will be carried out based on the LC-Q-TOF-MS technology. Targeted chemical isolation and structure elucidation will be subjected for further anti-neuroinflammatory evaluation, structure active relationship and function mechanism research. Results obtained from this project are expected to provide innovative researching idea, methods, and theoretical foundation to the discovery and development of anti-neuroinflammatory agents with high activity and specificity.