前期临床研究显示同型半胱氨酸与冠心病的不稳定性有关，内质网应激（ERS）、NLRP3炎性小体参与血管炎症，与动脉粥样硬化易损斑块形成有关，而1-磷酸鞘氨醇（S1P）可抑制ERS介导的炎症。预实验显示同型半胱氨酸干预巨噬细胞后，ERS、NLRP3表达上调，巨噬细胞凋亡增加，而S1P被抑制。因此我们推测：外源性S1P可通过抑制ERS介导的NLRP3炎性小体途径，抑制同型半胱氨酸诱导的动脉粥样硬化易损斑块的形成。为验证假说，建立同型半胱氨酸诱导ApoE-/-动脉粥样硬化小鼠形成易损斑块模型，通过使用外源性S1P，联合外源性S1P，ERS诱导剂、抑制剂，NLRP3过表达、干扰等干预措施，比较小鼠动脉粥样硬化斑块易损度，ERS，NLRP3、炎症因子表达，并在体外细胞实验中验证，阐明S1P通过ERS-NLRP3途径抑制同型半胱氨酸所致的易损斑块形成的机制。为急性冠脉综合征的防治提供新的干预靶点。

Our previous clinical research have shown that homocysteine affect the stability of coronary heart disease, endoplasmic reticulum stress(ERS)、NLRP3 inflammasome are involved in vascular inflammation, associated with atherosclerotic plaque vulnerability, and sphingosine 1-phospate (S1P) can inhibit ERS mediated inflammation. previous experimental suggest that after the macrophages was treated by homocysteine, ERS and NLRP3 expression, macrophage apoptosis are increases, and the expression of S1P is inhibited. We hypothesized: S1P can regulate ERS-mediated NLRP3 inflammasome, suppress the unstable atherosclerotic plaque induced by homocysteine. To test our hypothesis, establish the atherosclerotic plaque instability mice model by homocysteine induced ApoE -/- mice, By using interventions of exogenous S1P, joint use of exogenous S1P, ERS inducer and inhibitor, NLRP3 overexpression and interference, compare the artery plaque vulnerability, ERS, NLRP3 and vascular inflammatory factors expression; and in vitro validation experiments. Clarify the S1P regulate ERS-mediated NLRP3, inhibited the homocysteine-induced plaque instability. Provide new targets for intervention for the prevention of acute coronary syndrome.