项目名称： 基于同步辐射3D显微表征技术研究XBP1s对脑缺血后血管新生的作用及调控机制

项目编号： No.81501025

项目类型： 青年科学基金项目

立项/批准年度： 2016

项目学科： 医药、卫生

项目作者： 张萌琦

作者单位： 中南大学

项目金额： 17.5万元

中文摘要： 脑缺血后可引发自体血管新生，促进内源性血管新生以改善缺血区血供是脑卒中治疗修复的关键。我们前期应用同步辐射显微血管3D成像方法联合2D组织形态学技术，发现血管新生在脑缺血后极早期即可启动，并迅速达到高峰，新生血管迂曲度增加。最新研究表明内质网应激反应的重要转录因子XBP1s亦可作为血管新生的正向调控因子，与经典促血管生成信号通路间存在crosstalk，但其在脑缺血后血管新生中的作用和调控机制尚不明确。本项目拟通过构建慢病毒载体，于体外脑微血管内皮细胞糖氧剥夺模型和体内大鼠大脑中动脉阻塞模型进行定向转染，通过上调或下调XBP1s的表达,观察其对脑缺血后血管新生及下游靶基因表达的影响。经由细胞、动物双重模型，力求从结构-功能角度揭示XBP1s 与脑缺血后血管新生的作用关系，为阐明XBP1s调控脑缺血后微血管网络重塑的生物学机制提供理论基础和实验依据，以期为脑卒中的药物治疗提供新的干预靶点。

中文关键词： 同步辐射；脑缺血；XBP1s；血管新生

英文摘要： Cerebral ischemia induces spontaneous angiogenesis.To promote endogenous angiogenesis is a key factor of stroke treatment and rehabilitation.Using synchrotron radiation technique in combination with histomorphologic methods,our previous studies have demonstrated that the process of angiogenesis initiates in an early stage and quickly reached the culmination. Newly generated microvessels showed an increase in tortuosity and branching, thus intertwining into a complicated network.According to recent studies,the transcription factor XBP1s in endoplasmic reticulum stress response may also positively regulate angiogenesis,thus performing crosstalk with classic pro-angiogenic signal pathway.However,up to now,it still remains unclear about its role and regulatory mechanism.In the present study, we plan to perform directional transfection of lentivirus vectors to oxygen-glucose deprivation model in vitro and middle cerebral artery occlusion model in vivo. Via up-regulation or down-regulation of XBP1s expression,the parameters of the angiogenesis will be examined, as well as the downstream target gene expression.Based on studies both in vivo and vitro, this research aims to figure out the positive effects and reveal the relationship between the XBP1s treatment and angiogenesis after cerebral ischemia, proceeding to elucidate the upstream XBP1s regulatory mechanism in the ischemic stroke process from the perspective of structure and function.All the above-mentioned investigations are expected to provide the theoretical basis and experimental evidences for the potential clinical application of the XBP1s as a novel gene-intervention therpeutic target in the mannagement of ischemic stroke.

英文关键词： synchrotron radiation;cerebral ischemia;XBP1s;angiogenesis