依达拉奉联合灯盏花素对脑缺血大鼠神经元、胶质细胞及微血管影响的体内、体外实验研究

项目名称： 依达拉奉联合灯盏花素对脑缺血大鼠神经元、胶质细胞及微血管影响的体内、体外实验研究

项目编号： No.31260254

项目类型： 地区科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 吴春云

作者单位： 昆明医科大学

项目金额： 52万元

中文摘要： 缺血性脑血管疾病是当前严重威胁人类健康的一类重要疾病。目前脑缺血治疗的新策略强调对NVU（即神经血管单元：由神经元、神经胶质细胞、微血管等组成的结构复合体）的整体保护。依达拉奉和云南地方特色药物灯盏花素分别有一定的神经保护作用，但两药联合对脑缺血NVU的整体作用及分子机制仍缺乏研究。本项目应用免疫组织化学、RT-PCR、Western（或ELISA）及细胞培养等技术，对两种药物联合治疗大鼠脑缺血后NVU各组成部分的病理变化及相互关系进行系统研究。体外实验拟采用在神经炎症起重要作用的小胶质细胞系（BV-2细胞），对两种药物干预后各种炎症介质如：TNF-α、IL-1β、ROS、NO表达的影响及其可能涉及的MAPKs和NF-κB信号通路进行探讨。预期将在阐明依达拉奉联合灯盏花素治疗脑缺血对NVU的整体保护及分子机制方面有新的发现，为临床两药联用提高脑缺血的治疗效果提供可靠的体内、体外实验依据。

中文关键词： 脑缺血；神经血管单元；依达拉奉；灯盏花素；大鼠

英文摘要： Cerebral ischemic disease with its high risk in causing debilitation is one the major cerebral vascular diseases affecting many especially the aged population. Indeed, the incidence of cerebral stroke is rising exponentially in recent years thus threatening the health of many globally. The neurovascular unit (NVU) in the brain is made up of neurons, astrocytes, microglia and cerebral microvessels. Collectively, they maintain the normal function of the brain. Thus, any perturbations to the unit such as an ischemic insult would invariably result in neuronal damage and hence the normal function of the brain. Hence, NVU and its subcomponents in cerebral ischemia would be the key therapeutic target for restoring the normal functions of the brain. This study is aimed to investigate the combined therapy effects of edaravone and breviscapine on NVU in the ischemic cortex in rats subjected to MCAO. To better understand the molecular mechanisms of both drugs, the study will be extended to in vitro investigation using BV-2 cells, a cell line of microglial cells which are known to play a pivotal role in neuroinflammation. Different investigative tools including immunofluorescence, RT-PCR, Western blot (also ELISA), cell culture etc will be adopted to assess the expression levels of various inflammatory mediators such as TNF

英文关键词： cerebral ischemia；neurovascular unit；edaravone；breviscapine；rat