易损斑块破裂继发血栓形成是急性冠脉综合征(ACS)的主要病因，单核/巨噬细胞（Mφ）焦亡是易损斑块发生发展的重要环节，如何通过调控单核/Mφ焦亡来稳定易损斑块是目前研究热点。我们预实验发现硫氧还蛋白2（Trx2）在ACS患者外周血单核细胞和高脂喂养小鼠骨髓单核细胞中表达显著下降，Trx2表达上调可抑制Mφ焦亡关键调节蛋白NLRP3的表达，同时发现MAPK通路相关基因（ASK1、JNK、p38）和焦亡相关基因表达均下调，而调控Mφ焦亡可稳定易损斑块。故提出假说：Trx2通过ASK1/JNK/p38信号通路调控Mφ焦亡，从而稳定易损斑块，减少ACS发生。我们拟：1.在细胞和动物水平通过基因过表达和沉默验证Trx2通过调控Mφ焦亡在易损斑块发生发展中的作用，2.阐明Trx2通过ASK1/JNK/p38通路抑制Mφ焦亡稳定易损斑块的作用机制。为防治ACS提供新的靶点。

The key cause of acute coronary syndrome (ACS) is the rupture of vulnerable plaque with secondary thrombosis. And the pyroptosis of monocytes/macrophages plays an important role during the development of vulnerable plaques. Recent studies suggest that it is one of the research hotspots to stabilize vulnerable plaques via regulating the pyroptosis of monocytes/macrophages. In preliminary experiments,We found that Trx2 was significantly down-regulated in mononuclear cells of peripheral blood from patients with ACS and bone marrow CD115+ mononuclear cells from ApoE-/- mice with high fat diet than that in control group respectively. In addition, we observed that up-regulation of Trx2 contributed to the reduced expression of pyroptosis-related key protein NLRP3 in macrophages. Meanwhile, we found out that MAPK-pathway-related genes(ASK1、JNKP、38) and pyroptosis-related genes were down-regulated in macrophage linage overexpressing Trx2, and the studies demonstrated that alleviating the pyroptosis of macrophages is conductive to stabilize vulnerable plaques. Therefore, We hypothesize that Trx2 can stabilize vulnerable plaques and reduce the occurance of ACS via regulating macrophages pyroptosis by ASK1/JNK/p38 signal pathway. We will carry out:1. to explore the detail roles of Trx2 during the development of vulnerable plaques via regulating the pyroptosis of macrophages both in vitro and in vivo, 2. to study the mechanism of Trx2 to stabilize vulnerable plaques through macrophages pyroptosis regulated by ASK1/JNK/p38 signal pathway. This study aims to provide a new target for the occurrence of ACS.