心血管疾病居人类死亡原因之首，其中冠心病又是最常见病因之一，急性心肌梗塞(AMI) 病人仅在我国就高达450万人，每年新发病50万人。AMI死亡率极高，如经及时抢救使血管再通后，跟随而来的是危害极大的再灌注损伤，其可以使心肌坏死范围扩大一倍甚至更高，致死率高达30%。全球最新研究成果确认先天免疫的TLR/MyD88信号通路在急性心肌梗死再灌注损伤（AMIRI）的发生发展中发挥极为关键作用。我们首创的氨基噻唑类小分子化合物MyD88抑制剂TJ-M2010-2可以特异性抑制MyD88激活，已在多种重大疾病显示出惊人疗效。本项目的前期研究结果显示TJ-M2010-2使心肌梗死范围缩小约70%，使病灶心肌中的各种炎症因子及炎性细胞极显著减少。在此课题中将进一步探讨MyD88抑制剂对AMIRI的治疗作用及机理，为临床防治AMIRI提供靶向治疗奠定理论基础。

Cardiovascular disease is on the top cause of human death list. Coronary disease is one of the most common causes. In China alone, there are 4.5 million cases of acute myocardial infarction (AMI), with a 500,000 cases of growing number in each year. AMI is a critical life-threatening condition. Recirculating the coronary artery is the only effective life-saving treatment. However, following the recirculation of the coronary artery, an immediate severe reperfusion injury (AMIRI) will occur, which contributes more than half of the infarction area and causes a 30 percent mortality rate . Global research evidences confirm that TLR/MyD88 signaling pathway plays a critical role in AMIRI. We have design and synthesized a small molecule MyD88 inhibitor, TJ-M2010-2 which has demonstrated astonishing effectiveness for the treatment of many notorious diseases. In this project, our primary results showed that the administration of TJ-M2010-2 reduces about 70 percent of the infarction area, with significantly less infiltration of immune cells and inflammatory cytokines. The purpose of this project is to investigate further effects and mechanisms of TJ-M2010-2 on AMIRI. This study will give more new insights into the target treatment for AMIRI.