从胶质细胞TAK1-NF-κB通路调控炎症反应失衡切入研究清脑滴丸对急性脑缺血的干预效应机制

项目名称： 从胶质细胞TAK1-NF-κB通路调控炎症反应失衡切入研究清脑滴丸对急性脑缺血的干预效应机制

项目编号： No.81202683

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： 刘雪梅

作者单位： 北京中医药大学

项目金额： 23万元

中文摘要： 炎症反应应激过度是急性脑缺血损害的关键因素，胶质细胞是炎症反应主要的效应细胞，TAK1作为NF-κB上游重要的信号蛋白，是NF-κB调节炎症反应的关键调控枢纽，本课题结合前期工作提出：急性脑缺血主要病因病机之一是火热（毒）互结血瘀，阻滞脑络，其机制可能与胶质细胞TAK1-NF-κB通路调控炎症反应失衡及分布变化相关，清热解毒，活血宣窍法是其有效的治则。体外培养c6胶质细胞缺糖缺氧损伤模型和整体线栓法致急性脑缺血大鼠模型，选用清脑滴丸进行干预，动态观察TAK1-NF-κB通路上下游关键因子表达的变化，以及在不同类型胶质细胞中时空变化，阐述急性脑缺血胶质细胞与TAK1-NF-κB信号通路介导炎症反应的相关性，确定NF-κB作用的靶细胞，明确清脑滴丸的作用靶点和调节整合效应机制，阐明方证效应的作用环节，为清脑滴丸临床药理学提供科学依据。

中文关键词： 急性脑缺血再灌注；炎症反应；胶质细胞；NF-κB信号转导通路；清脑滴丸

英文摘要： Inflammatory response plays a critical factor in the process of acute cerebral ischemic damage. Gliacytes are the major effect cells in the cerebral inflammatory response. TAK1 is an important signaling protein of upstream of NF-κB, and the central link of NF-κB mediating inflammatory response. This subject is based on previous work and propose: One of the acute cerebral ischemical etiology and pathogenesis is hot (poison) and blood stasis blocking brain, its mechanism maybe the associated with imbulance and distribution of TAK1-NF-κB pathway mediating inflammtory response in gliacytes, The method of clearing heat-toxin and promoting blood circulation for removing obstruction in collaterals is an effective therapeutic approach.Culuring c6 glial cells lacked of glucose and oxygen induced cell damged model, focal cerebral ischemia made by suture occlusion technique induced middle cerebral artery occlusion in rats. Selecting Qingnao Dropping Pill intervention. Dynamic observing changes of the key facors in down stream of NF-κB signaling pathway, Further studying time and distribution of the NF-κB in different types of gliacytes. Clarifying the correlation between TAK1-NF-κB signal pathway mediated inflammatory response in gliacytes and acute cerebral ischemia, Defining the role of NF-κB target cells. Expliciting

英文关键词： acute cerebral ischemia-reperfusion；Inflammatory response；Glial cells；NF-κB signal transduction pathway；Qingnao dripping pills