CLIC1在动脉粥样硬化过程内皮细胞损伤与炎症中的作用及丹参酮ⅡA的干预

细胞内氯离子通道蛋白1（CLIC1）被认为是氧化应激中的传感器和效应器，在细胞氧化等因素刺激后其结构发生改变并插入脂膜中充当氯离子选择性通道，导致细胞内氯离子浓度增加。为了明确CLIC1在内皮细胞损伤与炎症中的作用及丹参酮ⅡA保护内皮损伤的机制，我们拟通过动物实验观察动脉粥样硬化动物中CLIC1的表达、膜定位及内皮细胞功能变化，并利用siRNA及转基因技术，建立CLIC1低表达及高表达的HUVEC细胞系，经过氧化氢诱导后用丹参酮ⅡA进行处理，检测细胞中CLIC1的表达及膜定位、细胞内氯离子浓度和iNOS、ET-1、ICAM-1、VCAM-1的表达及炎性因子TNF-α、IL6的分泌变化，明确CLIC1参与血管内皮细胞损伤与炎症的作用，并从CLIC1调控角度深入探讨丹参酮ⅡA抗动脉粥样硬化的机制。课题的实施可望为动脉粥样硬化的防治提供一种新思路，为抗动脉粥样硬化药物的筛选提供新靶点。

Chloride intracellular channel protein 1 (CLIC1) is considered to be oxidative stress sensors and effectors , and its structure is changed after oxidation stimulating factor and inserted into the cell membrane lipid acts as chloride ion selective channels , which result in the increasing intracellular chloride ionic concentration. In order to clarify the role of CLIC1 in the damage and inflammation of endothelial cell and the protect mechanism of Tanshinone ⅡA, we intend to observe the expression and location of CLIC1 and the change of endothelial cell function. In addition, the HUVEC lines in which CLIC1 express decreased or increased were established through RNA interference technology and transgenic technology. These cells were induced with hydrogen peroxide and treated with TanshinoneⅡA. CLIC1 expression and membrane localization, concentration of intracellular chloride, expression of iNOS, ET-1, ICAM-1, VCAM-1, the secretion of IL6 and TNF-α were detected. This project illuminate the function of CLIC1 in oxidative damage of endothelial cells, and uncovered the mechanism of anti- atherosclerosis of Tanshinone ⅡA from the perspective of CLIC1. The result of this project can provide a new target for anti- atherosclerosis research.