“剪切应力-Fractalkine/CX3CR1协同调控血管内皮细胞炎症反应的机制研究

项目名称： “剪切应力-Fractalkine/CX3CR1协同调控血管内皮细胞炎症反应的机制研究

项目编号： No.11462022

项目类型： 地区科学基金项目

立项/批准年度： 2015

项目学科： 数理科学和化学

项目作者： 聂永梅

作者单位： 新疆医科大学

项目金额： 52万元

中文摘要： 新疆是我国心血管病高发地区, 心血管疾病的发病率和死亡率呈逐年快速上升趋势。血管内皮细胞炎症激活是动脉粥样硬化等多种心血管疾病的共同病理生理基础，趋化因子Fractalkine及其高亲和力受体CX3CR1表达是多种炎症性疾病的始动环节。课题组前期体内外实验结果显示：动脉粥样硬化模型的血管低剪应力区域内皮细胞FKN/CX3CR1早期上调表达，且FKN/CX3CR1表达水平与动脉粥样硬化进程密切相关；低剪切应力作用亦可呈时间-强度依赖性地上调体外培养内皮细胞FKN/CX3CR1的表达。本项目拟进一步探讨剪切应力-FKN/CX3CR1协同如何调控血管内皮细胞炎症反应的相关分子事件，着重分析FKN/CX3CR1→G蛋白→NF-κB→内皮细胞炎症介质、趋化因子、粘附分子表达这条分子信息传递的力学生物学机理，为动脉粥样硬化等疾病的机制研究以及选择有效的早期诊断、预防和药物治疗的分子靶点奠定基础

中文关键词： 流体剪切应力；Fractalkine/CX3CR1；协同调控；血管内皮细胞；炎症反应

英文摘要： The epidemiological data show that Xinjiang Region of China is considered a high incidence of cardiovascular disease,and the morbidity and mortality rate are remarkably increaseded in the lately years. Inflammatory activation of Vascular endothelial cell is a common pathological and physiological basis of atherosclerosis and other diseases. Chemokine Fractalkine and its high affinity receptor CX3CR1 expression plays a key role in the pathogenesis of various inflammatory diseases. Previous in vitro and in vivo experimental results show : vascular endothelial cells of the atherosclerotic model in low shear stress area express FKN/CX3CR1 upragulation in early, and the expression level of FKN/CX3CR1 and atherosclerosis is closely related to the process; low shear stress may also be a time - intensity dependent upregulation of endothelial cells cultured in vitro FKN/CX3CR1.To further explore the shear stress - FKN/CX3CR1 collaborative how to regulate vascular endothelial cell injury induced by the project, focuses on the analysis of FKN/CX3CR1→G protein→NF-κB, inflammatory mediators, chemokines, adhesion molecules expression of endothelial cells, this information transmission path, for the early diagnosis of diseases, such as early prevention and treatment of atherosclerosis to provide new ideas and an important therapeutic target.

英文关键词： shear stress;Fractalkine/CX3CR1;synergistic regulation;vascular endothelial cell;inflammatory response