缺血再灌注损伤严重影响肝脏移植预后，肝脏窦内皮细胞（LSEC）是调控炎症细胞趋化及肝窦微循环障碍的关键节点。我们前期观察到活性氧能够诱导LSEC表面的TIM-3分子；阻断TIM-3会导致LSEC过度激活；TIM-3的表达受腺苷受体A2aR的调节。但TIM-3在LSEC缺氧应激中发挥的作用及其机制仍未明确。在大脑免疫细胞中有研究发现HIF-1能够结合TIM-3的启动子区域调控TIM-3表达，而另一项研究证实视网膜内皮缺氧后腺苷受体A2aR活化能够促进HIF-1α表达。因此我们提出假设：缺氧导致的A2aR活化能够通过转录因子HIF-1α影响LSEC表面TIM-3的表达，并进一步调控LSEC的活化和肝窦微循环状态。本项目拟在前期研究基础上，以TIM-3的功能及其活化途径为切入点，探讨A2aR/HIF-1/TIM-3通路在LSEC中可能的作用机制，为临床减轻肝脏IRI损伤提供新的理论依据和策略。

Liver sinusoidal endothelial cells (LSEC) are the first barrier to hypoxia injury and play an important role in maintaining the sinusoidal microcirculation homeostasis. Our previous study implied that TIM-3 might be involved in the activation of LSEC during hypoxia injury. A recent study has demonstrated that HIF-1 in mouse brain immune cells can bind to the promoter region of TIM-3 gene and regulates local inflammatory responses by activating TIM-3. While another study confirmed that activation of adenosine receptor A2aR can promote HIF-1α expression after retinal endothelial hypoxia. Therefore, we use the conditional gene knockout mice in liver IRI model to explore the role of A2aR/HIF-1/TIM-3 signaling pathway. The mechanism underline could provide a new strategy for clinical treatment of hepatic ischemia reperfusion injury.