新生儿缺氧缺血性脑病（HIE）是新生儿期严重疾病，发病率高，后遗症重，临床无特异治疗手段，一直是围生医学、神经科学等多学科研究的热点和难点。缺氧缺血性脑损伤（HIBD）后血脑屏障（BBB）通透性增加是继发脑水肿加重脑损伤的病理基础。新生儿期未成熟的大脑中存在有别于成熟大脑的活跃血管内皮生长因子（VEGF）信号。我们前期研究发现该信号系统以特有的方式在缺氧后可减轻BBB通透性从而减轻脑水肿，但VEGF在此保护作用中的信号传递机制和调控机制不清楚。本课题中，我们将以VEGF及受体信号系统为切入点，通过建立不同日龄大鼠HIBD模型和在培养的脑内皮细胞中制作体外BBB模型，并通过诱导内源性VEGF分泌和体外使用VEGF，模拟体内缺氧缺血条件下VEGF的作用状态；从整体、细胞及分子水平研究VEGF信号系统在HIBD后BBB通透性改变中的作用机制及调控机制，为临床新生儿HIE的治疗提供理论指导。

Hypoxia-ischemic encephalopathy（HIE） is a rinatal period disease which has a bad strong impact on children growing development. This disease has high morbidity and badly sequela.There aren't any special useful treatment means in clinical now.Therefore, HIE is becoming a hot and difficult problem of many subjects research such as perinatology, pediatrics, neuroscience, etcetera. The increase in blood brain barrier(BBB) permeability after Hypoxia-ischemic brain damage （HIBD ）will induce cerebral edema and exacerbate injury. The newborn brain has active Vascular Endothelial Growth Factor(VEGF) signal which different from adult brain. In our prior period study,we have found that VEGF signal may confer a protective response to subsequent toxic exposure to hypoxia. The transmission of neural signal and cytologic fundament are not cleare. The project cut-in point to signal transfer systems of VEGF. We will make rats model of HIBD at different ages. BBB endothelial cellmonolayers will be cultured for making BBB model in vitro. We will imitate VEGF signal in internal environment after HIBD by inducing endogenous VEGF secreting and by using VEGF in vitro. We will study the mechanisms of VEGF signal system which influence BBB permeability after HIBD at different levels such as the whole level,cellular level,molecular level . We will try to clarify the protective regulation mechanisms of VEGF signal transfer systems on BBB permeability after HIBD ,and to provide scientific basis for treatment of HIE.