巨噬细胞清除凋亡细胞功能障碍所导致的凋亡细胞聚集及继发性坏死是动脉粥样硬化（AS）不稳定斑块形成和进展的重要环节。LC3相关吞噬作用（LAP）是巨噬细胞新的吞噬形式，可高效清除凋亡细胞。ERK5失活可通过损伤部分LAP相关分子表达等途径，抑制LAP加剧AS的进展。中医毒邪贯穿AS整个过程，为其变证丛生的关键因素，解毒可对AS的治疗带来益处。我们前期研究发现，黄连解毒汤能延缓AS的进展，其机制与活化ERK5，促进Axl（可调控LAP相关分子的表达）和LAP相关分子TIM4的表达，增强巨噬细胞清除凋亡细胞有关。因此，我们提出黄连解毒汤可能通过活化ERK5增强巨噬细胞LAP的功能，发挥抗AS作用的假说。本项目体内外实验采用ERK5-MKO/ApoE-/-小鼠和ERK5-/-巨噬细胞株，进一步探索ERK5通过调控LAP参与AS病理过程的机制以及黄连解毒汤的干预作用，为中医从毒论治AS提供科学依据。

Apoptotic cells aggregation and secondary necrosis caused by clearance dysfunction of apoptotic cells by macrophage are important pathological links for the formation and progression of atherosclerosis (AS) unstable plaques. LC3-associated phagocytosis (LAP) that is a new phagocytic forms of macrophages can efficiently remove apoptotic cells. ERK5 inactivation can inhibit LAP by damaging the expression of some LAP-related molecules, and further aggravate the progress of AS. Pathogenic toxin is the key factor that cause the delay and complexity of AS, which runs through the whole process of AS. Intervention against pathogenic toxin can bring benefits to the treatment of AS. Our preliminary studies found that Huanglian Jiedu Decoction can delay the progress of AS, and its mechanisms are related to activating ERK5, promoting the expression of Axl which can regulate the expression of LAP-related molecules and TIM4 which is LAP-related molecules, and enhancing the clearance of apoptotic cells by macrophages. Therefore, we propose the hypothesis that Huanglian Jiedu Decoction plays an anti-atherosclerosis role by activating ERK5 to enhance LAP function of macrophages. In this project, ERK5-MKO/ApoE-/- mice and ERK5-/- macrophage strains are respectively used in in vivo and in vitro experiments to further explore the mechanism of ERK5 participating in AS pathological process by regulating LAP and the intervention effect of Huanglian Jiedu Decoction, thus providing scientific evidence for treating AS from pathogenic toxin.