心肌缺血再灌注（I/R）损伤是导致心血管病患者并发症发生和死亡的主要原因之一，通过预处理（PC）启动内源性保护机制是减轻I/R的有效措施。我们的前期研究发现氙气PC能通过抑制炎性反应显著减轻心肌I/R损伤，但作用可被血管内皮生长因子受体1（VEGFR1）阻断剂阻断，提示氙气可能通过VEGFR1发挥保护作用。本课题拟通过细胞培养模型研究氙气预处理在白细胞和内皮细胞VEGFR1表达中的作用机制；采用体外细胞培养及离体心脏灌注模型，研究氙气通过上调白细胞和内皮细胞VEGFR1表达对炎性反应的调控作用及机制；并在整体动物上阻断或激活VEGFR1，验证氙气通过上调VEGFR1，从而抑制炎性反应，减轻缺血再灌注损伤。本课题不仅为临床和基础研究使用氙气预处理提供依据，更重要的是，本课题将通过探索I/R中VEGFR1介导的炎症反应通路，为寻找新的治疗靶点及保护措施提供初步的理论依据。

Ischemia/reperfusion (I/R) injury is one of the main reasons of mortality and morbidity in the people suffered with cardiovascular disease. Preconditioning (PC) to evoke endogenous protection mechanism is the most effective therapy for I/R. Our pilot studies suggest that xenon PC contributes to protection from myocardial I/R injury via inhibiting inflammation. However, this protective effect can be eliminated by vascular endothelial growth factor receptor-1 (VEGFR1) blocker, suggesting xenon may exert its protective effects via VEGFR1. Interestingly, VEGFR1 was expressed on both leukocyte and endothelial cell, which participate in the inflammation via inflammatory factors up-regulation and their adhesion during myocardial I/R. We hypothesized, therefore, both leukocyte and endothelial cell were the target cells of xenon PC. In this research, VEGFR1 expression on both leukocyte and vascular endothelial cell (VEC) after I/R and/or xenon PC will be observed. Then using cell culture model and rat model of myocardial I/R in vitro, we test if xenon modulates inflammatory response via up-regulation of VEGFR1 in both leukocyte and VEC. To identify the role of VEGFR1 in myocardial I/R in vivo, VEGFR1 will be inhibited or activated before xenon PC, then inflammatory factors, leukocyte recruit in tissue, and myocardial function will be evaluated after I/R injury. Achievement of this project will provide a theory with xenon PC against myocardial I/R injury for clinic. More importantly, the involved mechanisms of VEGFR1 mediated inflammatory response pathway may contribute to finding new therapeutic target and protective strategies for I/R injury.