钙激活氯通道ANO1在ox-LDL诱导单核及巨噬细胞活化中的作用研究

项目名称： 钙激活氯通道ANO1在ox-LDL诱导单核及巨噬细胞活化中的作用研究

项目编号： No.81500363

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： 王炳香

作者单位： 泰山医学院

项目金额： 18万元

中文摘要： 动脉粥样硬化严重危害人类健康。由单核巨噬细胞迁移及活化介导的血管炎症反应在动脉粥样硬化的发生阶段至关重要。最新研究发现钙激活氯通道ANO1参与气道上皮炎症反应的调节，而与单核巨噬细胞介导的血管炎症反应之间的关系尚未见报导。我们的研究结果表明ANO1在THP-1源性巨噬细胞中表达并影响巨噬细胞炎症因子的分泌功能；ox-LDL（致动脉粥样硬化因子）能够显著提高ANO1在THP-1源性巨噬细胞中表达。我们推测：ANO1可能促进ox-LDL诱导的单核巨噬细胞迁移及活化，参与血管炎症反应。为证实该假说，我们拟以人THP-1及其诱导分化的巨噬细胞作为实验模型，采用分子生物学、膜片钳及基因干扰等技术，从细胞和分子水平来探讨ANO1与单核巨噬细胞迁移及活化所介导的炎症因子分泌功能之间的关系，通过调节ANO1功能性表达来预防单核巨噬细胞介导血管炎症的发生，从这一角度入手，为动脉粥样硬化的防治提供新的靶向。

中文关键词： 钙激活氯通道；ANO1；巨噬细胞；血管炎症；动脉粥样硬化

英文摘要： Atherosclerosis seriously harms human health. Vascular inflammation mediated by monocyte migration and macrophage activation is crucial in the development of the atherosclerosis. Recent study has found that ANO1, a calcium activated chloride channel, can regulate the inflammatory response in the airway epithelium. However, the relationship between ANO1 and the vascular inflammation mediated by macrophage has not been reported. Our study shows that ANO1 is expressed in the human THP-1 cells-derived macrophage and affects the secretion of inflammatory factors; Ox-LDL, a atherogenic risk factors, can significantly enhance expression of ANO1 in macrophages derived from human THP-1 cells. Therefore, we speculate that ANO1 might participate in the vascular inflammation by promoting monocytes migration and macrophages activation. Using human THP-1 cells and advanced scientific research methods (including molecular biology, patch clamp, confocal imaging and genetic interference technology, ect.) , we will explore the relationship between ANO1 and monocyte migration or macrophage activation thereby to provide a new mentality and a new therapeutic target for prevention and treatment of atherosclerosis.

英文关键词： calcium-activated chloride channels;anoctamin 1;macrophage;Vascular inflammation;atherosclerosis