以TNF-α和IL-1β为靶点超声分子成像及靶向治疗在动脉粥样硬化病变中的实验研究

项目名称： 以TNF-α和IL-1β为靶点超声分子成像及靶向治疗在动脉粥样硬化病变中的实验研究

项目编号： No.81501486

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： 王月丽

作者单位： 首都医科大学

项目金额： 18万元

中文摘要： 炎症贯穿整个动脉粥样硬化（AS）的发生发展过程，是促进AS进程、易损斑块形成及破裂、血栓形成和血管阻塞，引起急性心血管事件的关键因素。但是，由于易损斑块具有隐匿性和突发破裂的等特点，针对AS发生发展、易损斑块形成的早期预警及积极有效的抗炎治疗AS防治至关重要。肿瘤坏死因子α（TNF-α）和白细胞介素-1β（IL-1β）均是参与炎症反应的重要的始动炎症因子，是促进AS发生发展、易损斑块形成及破裂的关键分子。本申请拟使用APOE-/-小鼠，通过超声显微镜、超声微泡分子成像前沿技术在分子水平动态、无创显示并定量、定性AS斑块；采用分子生物学、病理组织学等实验方法结合体外分子研究探讨TNF-α和IL-1β靶向治疗对AS的作用及机制。本研究将借助以上实验方法，阐明以TNF-α和IL-1β为靶点超声分子成像及靶向治疗在AS早期预警和治疗中的应用前景及分子机制，为临床早期诊断和防治提供新的策略和思路。

中文关键词： 动脉粥样硬化；超声微泡；超声诊断；靶向治疗；炎症

英文摘要： Inflammation is involved in the development and progression of atherosclerosis (AS). As the key factor of acute cardiovascular events, it promotes vulnerable plaque rupture, thrombosis, and vascular occlusion .However, for vulnerable plaque is latent and has the feature of unexpected rupture, it is especially important for the prevention and treatment of atherosclerosis to take positive and effective anti-inflammatory measures and the early assessment of morphology and properties of atherosclerosis plaque. Tumor necrosis factor α(TNF-α) and interleukin-1β(IL-1β) are the two major initiating inflammatory cytokines in the inflammatory response, promoting the development of AS, vulnerable plaque formation and rupture. We will use APOE-/- mice undergoing ultrasonic microscopy, ultrasound microbubble molecular imaging targeted contrast agents for displaying AS plaque at the dynamic, non-invasive, and quantitative molecular level. Moreover, to evaluate the role and mechanism of TNF-α and IL-1β targeted therapy for AS , the molecular biology, histopathology and other experimental methods in vitro will be used. This study will elucidate the application prospects and molecular mechanism of TNF-α and IL-1β targeted ultrasound microbubble molecular imaging and therapy in the AS early warning and treatment, and to provide a new strategy and thinking for the early clinical diagnosis and treatment.

英文关键词： atherosclerosis ;ultrasound microbubble ;ultrasonic diagnosis ;targeted therapy;Inflammation