甲型流感病毒性肺炎并发严重的肺水肿，严重威胁人类的健康。课题组前期工作发现S1P2受体在血管内皮细胞中高表达，增强血管内皮细胞间黏附连接蛋白的表达，抑制血管通透性。但是S1P2受体对病毒性肺炎并发的肺水肿的作用及机制尚不清楚。本课题针对流感病毒性肺炎肺血管内皮细胞损伤而导致的肺水肿问题，拟通过采用流感病毒亚甲型FM1鼠肺适应株滴鼻感染野生鼠和S1P2基因敲除鼠，建立甲型流感病毒性肺炎的动物模型，观察比较野生型小鼠与JTE（S1P2受体高效拮抗剂）处理小鼠及S1P2基因敲除鼠的肺水肿和肺炎反应程度；通过体外肺血管内皮细胞实验，观察S1P2受体对肺血管内皮细胞通透性及炎症反应的作用；检测S1P2受体与内皮细胞MAPK和PI3K信号通路的相关性，阐明S1P2受体在病毒性肺炎中的作用与机制，为临床治疗流感病毒性肺炎提供更有价值的理论与实验依据。

Pandemic influenza virus A (H1N1) was associated with a higher risk of viral pneumonia resulting the pulmonary edema. Our previous study found that sphingosine-1-phosphate receptor 2 is highly expressed on endothelial cells. S1P2 receptor can enhance the expression of VE-cadherin, thus inhibit the vascular permeability. However, the effect S1P2 receptor on virus induced pneumonia is unknown. In this study, we focus on the the effect and mechanisms of S1P2 receptor on mouse H1N1 influenza virus induced pneumonia, we proposed to use C57BL/6 wild type mice and S1P2 receptor knockout mice, model of viral pneumonia in mice were replicated by inhaling FM1 via mice's noses, then we compare the extent of pulmonary edema in saline wildtype group, saline S1P2 receptor knockout group, FM1 wild type group, FM1 S1P2 knockout group, FM1 wild type group administrated with JTE-013 (S1P2 receptor antagonist). We also compare the vascular permeability of mouse lung endothelial cells in each group. We plan to study the MAPK and PI3K pathways to investigate the effects and mechanisms of S1P2 receptor on mouse H1N1 influenza virus induced pneumonia. Our results may represent a promising strategy for virus pneumonia therapy.