再灌注治疗是有效缓解心肌缺血的方法，但是再灌注本身也会引起心肌细胞的死亡。心肌缺血再灌注损伤目前缺乏治愈方法，寻找新的治疗靶点具有重要意义。我们的前期研究发现，HIPK2在小鼠心肌梗死组织中表达上调；HIPK2敲除可以保护小鼠心肌缺血再灌注损伤。本项目将在动物水平（心肌特异性敲除小鼠和过表达小鼠）和细胞水平（氧葡萄糖剥夺/恢复诱导凋亡）明确HIPK2在心肌缺血再灌注损伤中的功能。在机制方面，我们的数据表明MDM2可能是HIPK2的下游分子。我们将明确HIPK2下游调控机制；阐释HIPK2如何调控MDM2。本项目将明确HIPK2在防治心肌缺血再灌注损伤中的作用及分子机制，为心肌缺血再灌注损伤的治疗提供新靶点。

In patients with myocardial infarction (MI), timely and effective myocardial reperfusion can reduce MI injury and limit MI size. However, reperfusion itself can induce cardiomyocytes death, known as myocardial ischemia/reperfusion(I/R) injury. It still lacks therapy for I/R injury, and the identification of novel therapeutic targets is highly needed. In our previous research, we found that the expression of homeodomain-interacting protein kinase 2 (HIPK2) was elevated in MI region. Furthermore, HIPK2 knockout could protect against I/R injury in mice. These data indicate that HIPK2 might be a potential therapeutic target for I/R injury. In the present project, we will firstly identify the role of HIPK2 in I/R injury based on both loss-of-function and gain-of-function experiments. I/R injury model will be used in vivo with HIPK2 knockout mice and HIPK2 transgenic mice. Oxygen glucose deprivation/recovery (OGD/R) induced cardiomyocytes apoptosis model will be used in vitro with HIPK2-overexpressing lentivirus and HIPK2-interference lentivirus infection. In mechanism, based on our data, we propose mouse double minute 2 homolog (MDM2) to be a downstream gene of HIPK2. Next, we will perform the rescue experiments in vitro and in vivo to elucidate the regulation of HIPK2 to MDM2 in I/R injury. Our project will prove the protective effect of HIPK2 inhibition upon I/R injury and provide a novel therapeutic target for I/R injury.