阻塞性睡眠呼吸暂停综合征（OSAS）的核心损伤是慢性间歇缺氧（CIH），长期损害可导致痴呆，其机制不明。慢性间歇缺氧促进血管新生使血脑屏障渗透性增加导致Aβ过度渗透可能是其机制之一。间歇缺氧可诱导神经组织内HIF-a表达增高，HIF-a可能调控DLL4/Notch信号通路促进血管新生。故申请者推测慢性间歇缺氧通过HIF-1a、HIF-2a调控DLL4/Notch信号通路促进血管新生导致痴呆。因DLL4/Notch信号通路在间歇低氧导致的血脑屏障渗透性增加中的作用未见报道，故本研究具有创新性。本课题拟在前期研究基础上继续从体内实验及体外研究采用基因敲减及过表达等方法探讨小鼠血脑屏障内皮细胞中HIF-1a、HIF-2a、VEGF表达情况，探讨间歇缺氧下DLL4/Notch信号通路的在促进血管新生中的作用，研究上述通路在间歇缺氧导致的认知功能障碍中的作用，为临床寻找可能的治疗靶点提供实验室依据。

The impair of obstructive sleep apnea syndrome (OSAS) is chronic intermittent hypoxia (CIH), which may causes dementia (AD). Chronic intermittent hypoxia promote angiogenesis make blood brain barrier permeability increase leads to A beta excessive penetration may be one of its mechanisms. The higher expression of HIF-a which is induced by CIH may control may control DLL4/Notch signaling pathway to promote angiogenesis. Therefore, we suggested that DLL4/Notch signaling pathway regulated by HIF-1a and HIF-2a higher expressed by CIH may promote angiogenesis lead to dementia. There is no report about the DLL4/Notch signal pathway in the increase of blood brain barrier permeability by the role of intermittent hypoxia, so the study is innovative. This study intends to continue to using gene knockout alpha study, in vitro and vivo experiments, to study the decreased and the expression of HIF-1alpha , HIF-2alpha and VEGF , explore the intermittent hypoxia on the downstream target genes influence the expression of DLL4 / Notch signal pathway, to study the role of the above pathways in angiogenesis, looking laboratory basis for potential therapeutic targets for clinical treatment.