脑静脉病变导致的脑损害正被关注和重视,如静脉性脑梗死、静脉性脑微出血等可导致偏瘫、痴呆、癫痫等严重后果。高血压作为脑血管病发生的重要危险因素，是否引起脑静脉病变及相关机制尚不清楚。研究表明，激活Notch信号后EphB4表达受到抑制。而EphB4可调控Cav1表达和活性，影响细胞迁移、静脉移植物管壁增厚等血管重构过程。我们的前期研究发现，高血压大鼠脑静脉管壁重构以胶原增生为主，同时其静脉内皮EphB4、p-Cav1蛋白表达降低。那么Notch-EphB4-Cav1通路是否参与高血压脑静脉的重构？我们拟在高血压大鼠模型，观察其脑静脉的功能和结构改变，并采用双光子显微鏡定位脑静脉在局部对相关基因进行基因沉默，探讨Notch、EphB4、Cav1及下游信号分子彼此间的相互关系；同时，在体外高血压细胞模型上，通过细胞基因敲除、免疫沉淀等技术，研究其分子机制，为高血压脑静脉病变的防治提供研究基础。

The brain injuries brought about by the cerebral venous lesions are receiving more and more attention, for example, cerebral venous infarction or hemorrhage could result in hemiparesis, dementia,epilepsy, and other serious consequences. As an important risk factor of cerebrovascular disease, the mechanism of hypertensive cerebral venous changes are remain unclear. Studies have shown that expression of EphB4 is down-regulated after activation of Notch signaling. Also, it is demonstrated that EphB4 can affect cell migration and the thickness of the vessels,through regulating the expression or activity of Cav-1. Our previous study found that the walls of the cerebral vein from the hypertensive rats are thickened,which are mainly collagen proliferation and deposition, and that EphB4 expression of the cerebral veins and p-Cav1 expression of the vein endothelial cells of are dowe-regulated. Then, if the Notch-EphB4-Cav-1 signaling is invovled in the mechanism or not? In our study,we aim to observe the structural and functional changes of the cerebral vein from hypertensive rats.Also we aim to explore the interlationships of Notchs, EphB4, Cav-1, and the downstream tagets by gene silencing of related genes oriented by a two-photon microscope. Further, by means of the technologies such as gene knockdown, immunoprecipitation and so on, we try to expound the specific molecular mechanism of underlying hypertensive cerebral venous disease in cell models, and hope to provide theoretical guidance and fundational study for new preventation and treatment of hypertensive cerebral venous diseases.