人载脂蛋白CIII引发小型猪动脉粥样硬化致病机理的研究

项目名称： 人载脂蛋白CIII引发小型猪动脉粥样硬化致病机理的研究

项目编号： No.31201761

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 生物科学

项目作者： 丁瑜

作者单位： 吉林大学

项目金额： 25万元

中文摘要： 动脉粥样硬化（Atherosclerosis，AS）及其并发症是导致人类死亡的"头号杀手"，而高脂血症是AS发生的主要诱因。小型猪因其心血管系统与人类极其相似，是研究AS的理想模型动物。载脂蛋白（apo）CIII对调节血浆脂质水平起重要作用，我们在研究自主建立的高表达人apoCIII高脂血症小型猪中发现其易发生AS，但apoCIII致AS发生的具体机制尚未明确。本研究将在前期工作基础上，利用高表达人apoCIII转基因小型猪诱发AS，并对其进行病理指标检测，利用基因芯片对主动脉斑块处的差异表达基因进行筛查，并对获得的主要差异表达基因进行验证，解析apoCIII介导AS发生的关键信号调控网络。研究结果可为揭示apoCIII功能及其在AS发生过程中的作用提供新的理论依据，对揭示AS的病因、发病机理，探讨基因治疗方法以及进行新药研发等具有重要的理论意义和医学价值。

中文关键词： 人载脂蛋白CIII；小型猪；动脉粥样硬化；Toll样受体10；白介素6

英文摘要： Atherosclerosis and its compilations are currently responsible for the "First Killer"in our worldwide, and hypertriglycridemia is the predominant cause for atherosclerosis. Miniature swine may be the most appropriate animal model because its cardiovascular system closely resembles that of human. The important role of apolipoprotein CIII is to modulate plasma lipid concentrations, and our preliminary experiment suggested that the self-established hypertriglycridemia miniature swine overexpressing human apolipoprotein CIII prefers to developing atherosclerosis,however,the specific mechanism involved in these responses to apoCIII is un resolved. In this study, we are going to use hypertriglycridemia miniature swine to induce atherosclerosis, then its pathology will be detected. Genechip will be employed to investigate the different expression patterns in aorta plaque , while the preferentially expressed gene will be validated in order to analyze signaling networks regulated by apoCIII in process of atherosclerosis. The results would provide new theoretical bases for highlighting the function of apoCIII and its role on atherosclerosis. Furthermore, this founding should be theoretical meaning for elucidating the cause of disease and pathologic mechanism. Ultimately, it would be medical sense to exert on gene therapy

英文关键词： human apolipoprotein CIII；miniature swine；atherosclerosis；TLR10；IL6