脾失健运痰瘀互结是AS发生发展的核心病机，脾虚为本，痰浊血瘀为标。脾失健运肠道菌群失调，LPS入血引发炎症反应促进AS发生发展。最新研究发现LPS诱导巨噬细胞糖代谢重编程引发炎症反应在AS斑块形成中发挥关键作用。课题组前期研究发现健脾祛痰化瘀法在防治AS性疾病中具有良好抗炎作用，但具体机制尚不清楚。本项目拟以ApoE-/-AS小鼠、IPEC-J2肠上皮细胞、RAW264.7巨噬细胞为研究对象，运用分子生物学、宏基因组学、GC-MS、超声高分辨率小动物超声、MicroCT等技术，以肠道菌群驱动巨噬细胞糖代谢重编程为主要切入点，探讨脾失健运肠道菌群失调LPS入血，影响巨噬细胞糖代谢重编程诱发炎症反应促进AS斑块形成分子机理，部分揭示脾虚痰瘀所致AS微观病理基础，并阐明健脾祛痰化瘀法效应机制。为筛选以肠道菌群调控巨噬细胞糖代谢重编程为有效靶点的中药及中西医结合防治AS提供新的策略及科学依据。

Dysfunction of spleen in transportation and stasis-phlegm are core pathogenesis of AS. Spleen deficiency is the basis, and stasis-phlegm is the sign. During the state of dysfunction of spleen in transportation, gut microbiota imbalance leads to high LPS levels and causes inflammation, which can contribute to AS. Recent studies found that LPS-induced macrophage glycometabolism reprogramming caused inflmamation, which played a key role in AS.The previous study of the research group found that inhibition of inflammatory response was an important mechanism for the prevention and treatment of AS by Spleen-Strengthening Phlegm-Dissipating Stasis-Removing therapy, but te specific mechanism is still unclear. This project is conducting ApoE-/-AS mice, IPEC-J2 intestinal epithelial cells, RAW264.7 macrophages as the research object, taking advantages of molecular biology, metagenomics, GC/MS, ultrasound high-resolution small animal ultrasound, Micro CT, and so on, using gut microbiota driving macrophage glycometabolism reprogramming as the starting point, we explore that during the state of dysfunction of spleen in transportation, gut microbiota imbalance leads to high LPS levels and influences macrophages glycometabolism reprogramming, and in turn, causes inflammation to contribute to AS. It partly reveals microscopic pathological basis of AS caused by Dysfunction of spleen in transportation and stasis-phlegm. And it also reveals the effect mechanism of Spleen-Strengthening Phlegm-Dissipating Stasis-Removing therapy. These contribute to provide new research strategy and experimental basis for digging the traditional Chinese medicine which is regarding gut microbiota driving macrophages glycometabolism reprogramming as effective targets and preventing and treating AS from integrative Chinese and Western Medicine.