易损斑块破裂和血栓形成是急性冠脉综合征（ACS）的主要发病机制。我们的前期研究发现：情志刺激导致易损斑块模型小鼠血浆及主动脉组织SDF-1/CXCR4轴表达失衡，其失衡与斑块易损性严重程度成正相关，但二者之间直接联系的分子靶点尚不明确。最近文献报道：趋化因子SDF-1/CXCR4可作为独立判断自噬水平的新基因生物标记物，SDF-1/CXCR4自噬轴是调节细胞焦亡的关键信号，而细胞焦亡是动脉粥样硬化（AS）内源性危险相关分子模式的开启者。据此我们提出“情志刺激通过SDF-1/CXCR4自噬轴介导的巨噬细胞焦亡加重AS斑块易损性”的研究设想。拟在整体和细胞水平复制易损斑块小鼠模型及体外AS模型，采用siRNA、腺病毒、分子生物学等技术，阐明SDF-1/CXCR4自噬轴调控巨噬细胞焦亡在情志刺激加重AS斑块易损性中的关键作用及其分子机制，为寻找早期识别易损斑块的特征性指标和干预靶点提供科学依据。

Plaque rupture and thrombosis compose the main pathogenesis of acute coronary syndrome. Our preliminary study found emotional stress was a crucial factor that caused vulnerable plaque formation and SDF-1/CXCR4 biological axis dysfunction in the plasma, platelets, aortas. And the dysfunction was positively correlated with the severity of plaque vulnerability. However, it remains unclear if there is a direct correlation between vulnerable plaque rupture and the SDF-1/CXCR4 signalling pathway in stressed mice. Recently, it’s reported that the chemokine SDF-1 and CXCR4, as new genetic biomarkers to judge the level of autophagy independently, are the key signal to regulate the function of pyroptosis, which is the initiator of endogenous risk related molecular model of atherosclerosis. Therefore, we bring forward the new assumption that emotional stress induces vulnerable plaque rupture via macrophage pyroptosis mediated by SDF-1/CXCR4 autophagy axis. We plan to establish a vulnerable plaque model in ApoE-/- mice and AS cell model in vitro, using the technology of siRNA, adenovirus, molecular biology, etc. We will reveal the pivotal role and the molecular mechanism which can clarify emotional stimulation aggravated AS plaque vulnerability via regulating macrophage pyroptosis mediated by SDF-1/CXCR4 autophagy axis. Our study will provide scientific evidence for therapeutic target and characteristic biological markers which can prevent vulnerable plaque early.