巨噬细胞内脂质代谢异常及其引起的动脉壁脂质累积是动脉粥样硬化发生发展的重要环节。糖基化终末产物（AGEs）及其受体（RAGE）的相互作用与糖尿病并发动脉粥样硬化的发生和发展密切相关，但其对巨噬细胞脂代谢的影响及机制至今仍未明确。本课题组前期研究结果表明AGEs-RAGE结合与糖尿病动脉粥样硬化早期病变相关，尤其影响动脉壁脂质累积，阿托伐他汀可以调控这一过程。据此，本研究将在THP-1细胞株及ApoE-/-小鼠模型中，应用AGEs进行干预，同时应用AGEs-RAGE阻断剂及阿托伐他汀进行调控，通过测定巨噬细胞内脂质累积程度，巨噬细胞脂质吞噬、合成、流出能力及其信号途径表达，来阐明AGEs-RAGE介导巨噬细胞内脂质代谢异常的作用及机制，并阐明他汀类药物对巨噬细胞脂质代谢异常的逆转作用及机制，为早期干预糖尿病心血管病变发生提供新靶点，并为他汀类药物防治血管病变的机制提供理论基础。

Abnormality of macrophage lipid metabolism and its induced arterial wall lipid accumulation is a key link in the development of atherosclerosis. Interactions of advanced glycation end products ( AGEs ) and its receptor ( RAGE ) closely related with development and progression of diabetes complicated atherosclerosis, , but its effect to macrophage lipid metabolism and its mechanism remains unclear. Our early results indicate that AGEs-RAGE interaction associated with early lesions of diabetic atherosclerosis, particularly affecting the arterial wall lipid accumulation, atorvastatin can control this process. Accordingly, this study will use AGEs to interfere in THP-1 cell line and ApoE - / - mice model, and applicate AGEs-RAGE blockers and atorvastatin for regulation and control. Through the determination of macrophage lipid accumulation , and the ability of macrophage for lipid phagocytosis, synthesis, efflux, and its signal pathway expression, We intend to elucidate the AGEs-RAGE mediated abnormal lipid metabolism in macrophage and its mechanism, and to elucidate the reverse effects of statins on macrophage lipid metabolism abnormalities and the mechanisms. We surpose to provide new targets for early intervention in diabetic cardiovascular complications, and provide a theoretical basis for statins on prevention and treatment of vascular lesions.