氢分子影响动脉粥样斑块稳定性及其巨噬细胞内质网应激凋亡途径的分子机制

项目名称： 氢分子影响动脉粥样斑块稳定性及其巨噬细胞内质网应激凋亡途径的分子机制

项目编号： No.81200216

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： 宋国华

作者单位： 泰山医学院

项目金额： 23万元

中文摘要： 稳定动脉粥样硬化（AS）斑块是抑制心脑血管病急症的重要手段。我们的前期工作发现，氢分子作为新兴的抗氧化和抗凋亡气体物质，能抑制AS斑块处的炎症反应和巨噬细胞聚集（发表在2012年"Atherosclerosis"杂志），提示氢分子能影响斑块稳定性。但氢分子抑制斑块稳定性的分子机制并不清楚。结合我们既往研究曾发现氧化低密度脂蛋白诱导的内质网应激（ERS）途径介导了巨噬细胞凋亡的事实，我们提出氢分子可能通过抑制巨噬细胞ERS的凋亡途径，进而影响AS斑块的稳定性。本项目拟在载脂蛋白E基因敲除AS模型鼠和巨噬细胞模型上，探讨氢分子对AS斑块稳定性的影响及氢分子对巨噬源性泡沫细胞凋亡的调控作用及其与AS进展的关系，并研究氢分子对CHOP和caspase-12等内质网凋亡相关分子表达的影响及其与巨噬细胞凋亡的关系。期待为氢分子应用于促进斑块稳定性减少心脑血管病急性事件提供坚实实验基础。

中文关键词： 动脉粥样硬化；氢气；斑块稳定性；脂蛋白；内质网应激

英文摘要： Stabilization of vulnerable plaques is an important direction in the treatment of cardiovascular and cerebrovascular disease. Our previous work, which published in "Atherosclerosis", has reported that hydrogen, an emerging anti-oxidative and anti-apoptotic gas, inhibits the inflammation process and macrophage accumulation in atherosclerotic lesions, indicating that hydrogen might have an effect on plaque stability. However, the molecular mechanisms remain elusive. Given the fact that our previous work confirmed oxidized low density lipoprotein-induced endoplasmic reticulum stress (ERS) mediates macrophage apoptosis, we hypothesized that hydrogen might regulate atherosclerotic plaque stability by inhibiting ERS-induced macrophage apoptosis. In this study, we aim to determine the effects of hydrogen on atherosclerotic plaque stability and confirm whether hydrogen regulates plaque stability by inhibiting the apoptosis of macrophage-derived foam cells in the models of apolipoprotein E knockout mouse and macrophage cell line. Moreover, we try to demonstrate whether hydrogen inhibits the apoptosis of macrophages by regulating the expressions of several ER stress-associated proteins, including C/EBP-homologous protein (CHOP) and caspase-12. We hope to provide the experimental basis for the application of hydrogen in st

英文关键词： Atherosclerosis；Hydrogen；Plaque Stability；Lipoprotein；Endoplasmic Reticulum Stress