二甲双胍对糖尿病前期合并缺血性脑卒中后认知功能的影响和机制研究

项目名称： 二甲双胍对糖尿病前期合并缺血性脑卒中后认知功能的影响和机制研究

项目编号： No.81200844

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 神经系统疾病、精神疾病

项目作者： 黎洁洁

作者单位： 首都医科大学

项目金额： 23万元

中文摘要： 我们的研究及预实验发现，缺血性脑卒中和2型糖尿病会引起AD样神经病理改变及认知功能障碍。糖尿病前期包括空腹血糖受损和糖耐量异常，是2型糖尿病发生前的预警信号。糖尿病前期是否会加剧缺血性脑卒中引起的AD样神经病理改变及认知功能障碍，能否通过针对糖尿病前期的治疗达到阻断缺血性脑卒中、糖尿病和AD间的联系？我们拟通过高脂饮食喂养制作糖尿病前期的大鼠模型，并通过线拴法实现大脑中动脉闭塞-再灌注。通过检测动物认知功能、神经功能，采用ELISA、Western-Blot、高尔基染色等方法观察Aβ42和神经结构改变的时序性关系，采用Western-Blot观察和Aβ42相关蛋白的表达以探索糖尿病前期合并缺血性脑卒中后脑内AD样神经病理生理进展的过程。通过腹腔注射二甲双胍及检测其对上述指标的影响，分析针对糖尿病前期的治疗是否可以改善糖尿病前期合并缺血性脑卒中后的认知功能、AD样的神经病理改变及其作用机制。

中文关键词： 卒中；糖尿病前期；预后；认知；二甲双胍

英文摘要： Our primary and pilot studies indicated brain ischemia and type 2 diabetes both induced AD-like neuropathology and impaired cognitive function. Pre-diabetes (also called diabetetic risk-raised status) which includes impaired fasting blood glucose and impaired glucose intolerance is considered as the early warning of diabetes. To date, it's not clearly understood what influence of pre-diabetes had on AD-like neuropathology and impaired cognitive function induced by brain ischemia. It's only the beginning to look for effective strategy to block the link between AD and brain ischemia or diabetes. An advanced method targeted pre-diabets to prevent the development of AD-like neuropotholy after brain ischemia has not been reported. In order to explore the AD-related pathological and biological process in rats with pre-diabetes and brain ischemia, male Sprague-Dawley rats would be fed with high-fat diet for 14 weeks to induce prediabetes and later on subjected to a 90-min right middle cerebral artery occlusion (MCAO). Not only the cognitive function, neurological function would be measured,but the expression of Aβ42 and the change of neurological structure would also be detected via ELISA,Golgi staining and Western-blotting assay.Besides those index, expression of Aβ42-related protein would be measured as well. Metfo

英文关键词： stroke；prediabetes；prognosis；cognition；metformin