巨噬细胞胞葬作用功能障碍导致的斑块内凋亡细胞聚集及继发性坏死是不稳定性斑块形成和破裂的重要因素。SUMO特异性蛋白酶1（SENP1）可能通过STAT3-SOCS3通路或ERK5等信号分子调控巨噬细胞的胞葬作用，影响动脉粥样硬化（AS）的发生发展。课题组前期研究发现，中药复方冠心康通过活化ERK5调控巨噬细胞胞葬作用，发挥抗AS的作用。因此，我们提出冠心康可能通过上调SENP1的表达，增强巨噬细胞的胞葬作用，达到抗AS作用的假说。本研究体内建立SENP1-/-/LDLR-/-小鼠AS模型，体外培养正常和SENP1缺失的巨噬细胞并用ox-LDL干预，模拟AS的部分病理特征，研究SENP1对巨噬细胞胞葬作用的影响及其参与AS病理过程的可能机制；同时观察具有益气活血、化痰降浊功效的冠心康的干预作用，阐明益气活血化痰法抗AS可能的作用机制，为中医药防治AS提供科学依据。

Aapoptotic cell aggregation and secondary necrosis within plaques caused by macrophages efferocytosis dysfunction are important factors for formation and rupture of unstable plaques.SUMO-specific protease 1 (SENP1) affects the development of atherosclerosis (AS) through regulating the macrophages efferocytosis via STAT3-SOCS3 pathways or ERK5 signals.Our previous studies have found that chinese medicine compound Guan Xin Kang(GXK) can regulate the macrophages efferocytosis by activating ERK5 to protect against AS.Therefore,we propose that GXK may resist AS via raising the expression of SENP1 to increase macrophages efferocytosis.In vivo,we we establish the SENP1-/-/LDLR-/- atherosclerotic mice model;in vitro,normal and SENP1-deficient macrophages are cultured and the macrophages are simulated with oxLDL to mimic the part of the pathological characteristics of AS.We study the effect of SENP1 on macrophage efferocytosis and the possible mechanism of SENP1 in the pathogenesis of AS.At the same time, we observed the effect of GXK with supplementing qi and activating blood circulation dissipating phlegm and descending the turbid on the experiments.The study will elucidate the possible mechanism of supplementing qi and activating blood circulation dissipating phlegm and descending the turbid to prevent AS, and provide a scientific evidence for the prevention and treatment of atherosclerosis by traditional Chinese medicine.