酪氨酸激酶受体B对内皮通透性的影响及其在动脉粥样硬化发生发展中的作用研究

项目名称： 酪氨酸激酶受体B对内皮通透性的影响及其在动脉粥样硬化发生发展中的作用研究

项目编号： No.81200209

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学一处

项目作者： 姜虹

作者单位： 山东大学

项目金额： 23万元

中文摘要： 动脉粥样硬化（AS）是冠心病等心脑血管病的主要病理基础，已严重危害人类健康。近年研究发现脑源性神经营养因子（BDNF）- - 酪氨酸激酶受体B（TrkB）通路在血管内皮细胞中表达，但其是否参与AS的病理过程尚未阐明。我们前期研究发现该通路涉及冠心病的发病及预后，为进一步研究其机制，本项目拟在体外培养的人主动脉内皮细胞和ApoE-/-小鼠体内，通过基因沉默和过表达TrkB，研究TrkB对血管内皮通透性的影响及机制；体外研究TrkB在炎性诱导的内皮高通透性中的作用及机制；进一步通过高脂喂养ApoE-/-小鼠构建小鼠AS模型，体内研究TrkB是否通过影响内皮通透性进而影响AS的发生发展。本研究旨在揭示TrkB对内皮通透性的调节作用和分子机制，为AS的防治开辟新思路。TrkB基因位于冠心病的易感区-染色体9P21区，因此本项目的预期结果有助于部分解释染色体9P21区与冠心病相关的分子基础。

中文关键词： 冠心病；动脉粥样硬化；内皮屏障功能异常；酪氨酸激酶受体B；内皮钙粘蛋白

英文摘要： Atherosclerosis is a pathological basis of cardiovascular diseases such as coronary heart disease, which is the leading cause of death globally.Enhanced vascular permeability is an early alteration in arterial function during the formation of atherosclerotic lesions. Increased permeability of the endothelium is believed to allow entry of lipoproteins into the vessel wall. Once present, lipoproteins become oxidized and exhibit chemotactic and proinflammatory properties, thus leading to monocyte accumulation, foam cell formation, and lesion formation. Mechanism of regulating endothelial permeability is unknown. Tyrosine kinase receptor B (TrkB) is a high-affinity receptor for brain-derived neurotrophic factor (BDNF). The BDNF-TrkB pathway has critical roles in the survival, growth, maintenance, and death of central and peripheral neurons. The pathway is also expressed in endothelial cells. However, its role in pathological development of atherosclerosis is unclear.We reported the association of the pathway and occurrence and prognosis of Coronary Heart disease. In present study, with small interfering RNA and lentivirus-TrkB, we will study effect of TrkB on endothelial permeability in vitro and in vivo; study role of TrkB in TNF-α-induced endothelial hyperpermeability; study effect of TrkB on lipid and macrophage

英文关键词： Coronary artery disease；Atherosclerosis；endothelial barrier’s dysfunction；tyrosine kinase receptor B；cadherin 5