Syk介导的力学信号通路在低剪应力致动脉粥样硬化中的作用

Carotid atherosclerosis is an important cause of ischemic encephalopathy. Previous studies suggested that atherosclerosis (AS) is closely related with the shear stress (SS). We speculate that low shear stress may activate Syk and affect expression of downstream signal pathways and related inflammatory cytokines by binding Platelet - endothelial cell adhesion molecule-1(PECAM-1) and Syk, and then induce arteriosclerosis. This study intends to make in-vitro experiments with parallel plate flow chamber, and experiments in-vivo with carotid atherosclerosis rabbits. The ultrasonic instrument which is special fitted for small animals is used to detect carotid sinus of rabbits. Shear stress distribution mapping software is used to detect spatial distribution of shear stress in carotid sinus. HE staining detect carotid artery plaque; EMSA detect NF-κB; Westernblot idetect IκB, ITIM phosphorylation of PECAM-1, Syk. ELISA detect IL-6 and IL-8; Atomic force acoustic microscope and laser scanning confocal microscopy are used to observe structure of cytoskeleton. Then the results of in-vitro and in-vivo experiments are analyzed comparatively. The purpose is to reveal the mechanism that low shear stress induce AS through Syk activation by binding PECAM-1 and Syk and then affect expression of downstream inflammation-associated factors, provide a new way for prevention and treatment of atherosclerosis.

颈动脉粥样硬化是导致缺血性脑病的重要原因。既往研究提示动脉粥样硬化（AS）和血流剪应力(SS)密切相关。我们推测：低SS触发血小板内皮细胞粘附因子（PECAM-1）与Syk结合，激活Syk，影响下游信号通路和相关炎症因子表达，诱发动脉硬化。本研究拟通过平行平板流动腔的离体实验、以颈动脉粥样硬化兔为模型的在体实验，使用小动物超声仪活体检测颈动脉窦部，用剪应力分布图绘制软件绘制颈动脉窦部剪应力空间分布图；HE染色检测颈动脉斑块；EMSA检测内皮细胞NF-κB表达；Westernblot 检测内皮细胞IκB、PECAM-1的ITIM磷酸化、Syk表达；ELISA检测IL-6、IL-8表达；原子力声显微镜、激光共聚焦显微镜检测细胞骨架。将在体和离体检测结果进行对照分析，揭示体内低SS通过触发PECAM-1与Syk结合，激活Syk，影响下游炎症相关因子表达,诱发AS的机理，为防治AS提供新方法。

颈动脉粥样硬化是导致缺血性脑病的重要原因。既往研究提示动脉粥样硬化（AS）和血流剪应力(SS)密切相关。本研究通过平行平板流动腔的离体实验、以腹主动脉血流减少建立大鼠腹主动脉低剪应力模型的在体实验，探讨Syk在低剪应力介导的PECAM-1信号通路中的作用。阐明了低剪应力通过触发内皮细胞Syk结合PECAM-1，激活Syk，继而影响下游炎症相关因子表达，引发动脉粥样硬化的机理，为防治AS提供新方法。