阻塞性睡眠呼吸暂停低通气综合征（OSAHS）是导致动脉粥样硬化（AS）的重要原因之一，但具体机制尚不清。慢性间歇性低氧（IH）是OSAHS是典型特征之一，也可能是OSAHS致AS的关键因素。晚期糖化终末产物受体（RAGE）-配体系统在AS发病机制中起着重要作用，而IH又能激活AGEs/RAGE系统。因此，本项目拟基于RAGE-配体系统探讨慢性IH致AS机制中的作用。首先，在体外实验中使用RNA干扰法沉默RAGE，检测IH 对THP-1巨噬细胞转化、泡沫细胞形成及胆固醇运输蛋白调节等的影响。接着，在动物实验中采用基因敲除等技术，检测IH对ApoE-/-或ApoE-/-/RAGE-/-基因敲除小鼠模型AS病变形成等的影响。从而为OSAHS致AS作用机制提供新的实验依据。

Obstructive sleep apnea-hypopnea syndrome (OSAHS) is one of the significant pathogenic factors for atherosclerosis (AS), but the definite mechanism is still unclear. Chronic intermittent hypoxia (IH) is one of the typical features of OSAHS, may also be a key factor for OSAHS to cause AS. The receptor for advanced glycation end products (RAGE)and its ligands system may play an important role in AS, and IH can also activate RAGE-its ligands system. Therefore, this project will explore the mechanisms of chronic IH on the development of AS, based on its effect on RAGE-its ligands system. Firstly, In vitro using RNAi to suppress RAGE, we will detect the effect of IH on THP-1 macrophage transformation, foam cell formation and cholesterol transport protein, etc. Then, In vivo, we will detect the effect of IH on AS lesions in ApoE-/- knockout mice and RAG-/-/ApoE-/- double knockout mice model. This project will provide new experimental data for the mechanisms for the effect of OSAHS on the development of AS.