腹主动脉瘤（AAA）是一种危及生命的主动脉退行性疾病。炎症反应和巨噬细胞浸润与AAA的形成密切相关，研究表明动脉粥样硬化（AS）过程中IL18不仅通过IL18r还通过新受体NCC诱导炎症信号参与AS的发生发展，但在AAA过程中NCC的表达和作用尚未明了。本项目拟构建巨噬细胞特异性敲除IL18r、NCC以及联合受体敲除的小鼠来制备AAA模型，研究巨噬细胞中IL18信号通路激活参与AAA发生发展的作用方式，并基于预实验结果运用细胞实验及动物模型进一步阐明血管周围脂肪组织（PVAT）通过分泌脂肪因子Leptin刺激巨噬细胞IL18介导的炎症信号通路而促进AAA形成的分子机制，为探索AAA的防治靶点提供实验室依据。

Abdominal aortic aneurysm (AAA) is a kind of life-threatening degenerative disease of the abdominal aorta, which is characterized by inflammatory reaction and macrophage infiltration. Studies have shown that IL-18 participates in the development of atherosclerosis (AS) not only through IL-18r but also through a new receptor, NCC to induce the inflammation signals. However, the expression and function of NCC are not yet known in the process of AAA. This project is aimed to use the macrophage-specific IL18r-deficient (Apoe–/–Il18rflox/floxLyz2-Cre), NCC-deficient (Apoe–/–Nccflox/floxLyz2-Cre) and IL18r- and NCC- compound deficient (Apoe–/–Il18rflox/floxNccflox/floxLyz2-Cre) mice to examine the participation of IL18r and NCC in mediating IL18 actions of macrophages in the pathogenesis of subcutaneous angiotensin-II (Ang-II) infusion-induced experimental AAA. Based on the preliminary results to further elucidate the molecular mechanism that perivascular adipose tissue (PVAT) contributes to the increase of AAA incidence by lipokine Leptin in the cultured cells and animal models, which promotes the IL18-mediated inflammatory signaling pathway in macrophages. This study will provide the laboratory basis for exploring the prevention and treatment targets of AAA.