心血管疾病是目前威胁人类健康的重要疾病。包括缺血/再灌和阿霉素等在内的多种损伤都会引起心肌细胞的死亡，进而引起心力衰竭等疾病。受体相互作用蛋白3（Receptor-interacting Protein Kinase 3, RIP3）在细胞的凋亡和坏死调节中发挥重要作用，已有的研究发现它在包括急性胰腺炎、炎性肠病、脂肪肝、阿尔茨海默病以及血管平滑肌异常增生等多种疾病的发生发展过程发挥作用。本研究希望研究RIP3在心肌细胞中的作用及相关机制。我们将首先在体内和体外水平，研究RIP3对心肌细胞凋亡和坏死的作用；而后我们将利用质谱和siRNA文库筛选等高通量技术，在心肌细胞中研究RIP3调节细胞死亡的相关信号通路；最后我们将对筛选出的信号通路进行验证和深入研究。本研究希望以RIP3为节点，进一步丰富心肌细胞死亡的调控网络，为临床心肌细胞损伤的预防和治疗提供新的药物设计靶点。

Cardiovascular disease is one of the leading causes of death in the world. Multiple insults including ischemia/reperfusion injury and doxorubicin can cause cardiomyocyte death and subsequent heart failure. Receptor-interacting protein kinase 3 (RIP3) is a key regulator of cell apoptosis and necrosis, which is involved in acute pancreatitis, inflammatory bowel disease, hepatosteatosis, Alzheimer's disease and abnormal vascular smooth muscle cell proliferation. Here, we hope to investigate the role of RIP3 in cardiomyocyte death and the related mechanisms. First, we will test the effect of RIP3 in cardiomyocyte apoptosis and necrosis in vivo and in vitro. Then we will seek the mechanisms with mass spectrum and siRNA library screening. And the targets will be further validated and investigated. With this study, we will integrate the network regulating cardiomyocyte survival and death, which will uncover novel therapeutic targets of cardiac injury.