基于“毒损脑络”学说研究苦参抗炎活性成分治疗老年痴呆的作用机制

项目名称： 基于“毒损脑络”学说研究苦参抗炎活性成分治疗老年痴呆的作用机制

项目编号： No.81460665

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 医药、卫生

项目作者： 李娟

作者单位： 宁夏医科大学

项目金额： 45万元

中文摘要： 本课题以老年痴呆发病的毒损脑络中医学说和慢性神经炎症西医理论之间的相关性为指导，首次提出从清热解毒抗炎中药中寻找治疗老年痴呆药物的新思路。在前期实验中我们发现清热解毒中药苦参的主要抗炎活性成分苦参碱对老年痴呆小鼠有显著治疗作用，并可抑制 Aβ诱导的小胶质细胞(Mic)炎症介质(内生之毒)的释放，使神经炎症反应起始靶点 FPR2表达下调，由此推测苦参碱通过抑制 FPR2 介导的神经炎症发挥抗老年痴呆作用。本研究拟采用经典的老年痴呆小鼠模型和 Mic 活化模型，运用高内涵、Westernblot、免疫组化等方法，旨在探究苦参碱抗老年痴呆作用是否通过抑制毒损脑络相关的神经炎症而实现，以及确证炎症起始靶点 FPR2 对该作用的介导。本研究将为从西医角度诠释中医的毒损脑络学说提供新思路、为确立 FPR2 作为老年痴呆治疗的新靶点和开发苦参碱的临床新用途提供科学依据。

中文关键词： 毒损脑络学说；神经炎症；苦参碱；老年痴呆；甲酰肽受体2

英文摘要： On the basis of the significant correlation between traditional injury of brain collaterals by toxins theory and western chronic neuroinflammation theory in the incidence of Alzheimer's disease(AD), we firstly suggest that Chinese medicine for detoxification which has anti-inflammatory effect could be used for the treatment of AD. Matrine is the main anti-inflammatory ingredient in the Chinese detoxification medicine sophora. Previous studies suggested that matrine had significant protective effect on learning and memory impairment in AD mice; it could also inhibit Aβ-induced inflammatory mediators (endogenous toxins in traditional Chinese medicine) release in microglial cells and down-regulate the expression of the initial receptor FPR2 in inflammation. Therefor we presume that matrine exhibit anti-AD effect by inhibiting FPR2 mediated neuroinflammation. In this study, AD mice and microglia activation model were employed; high content analysis, Western blot,PCR and immunohistochemistry were used for clarifying how matrine inhibit the injury of brain collaterals by toxins associated neuroinflammation in AD and discussing the role of FPR2 related signaling pathways in AD neuroinflammation. This study will provide a new idea for interpreting traditional injury of brain collaterals by toxins theory from western sight. It could also provide scientific basis for establishing FPR2 as a new target for AD treatment and developing new clinical applications for matrine.

英文关键词： Injury of brain collaterals by toxins theory;neuroinflammation;matrine;Alzheimer's disease;FPR2