颅内动脉瘤形成机制仍不清楚。课题组前期研究证实VE-cadherin磷酸化介导的血管内皮损害在动脉瘤形成中发挥重要作用。通过对VE-cadherin调控的相关因子进行系统分析，结合PKCα调控p120ctn磷酸化不仅影响VE-cadherin磷酸化和血管内皮稳定，且作为体内固有免疫重要调控因子参与血管内皮活化调控的科研实践，提出PKCα调控p120ctn磷酸化在调节血管内皮通透性和血管壁炎症反应两方面共同参与颅内动脉瘤形成的假说。本项目拟应用基因突变、基因干扰、抑制剂和萤火虫酶检测等技术，通过体内和体外实验，分别从动物和细胞水平探讨PKCα调控p120ctn磷酸化介导的NF-ΚΒ，Rho和MPO等信号通路在动脉瘤形成中的作用及调控机制，为探明颅内动脉瘤形成机制奠定实验基础和理论依据。

The formation of intracranial aneurysm is still unclear. It was confirmed by our previous study that vascular endothelial injury initiated by VE-Cadherin phosphorylation plays an important role in the formation of intracranial aneurysm.The association of p120catenin phosphorylation with VE-Cadherin shows that p120catenin phosphorylation at S879 disassemble VE-Cadherin junction and disrupt vascular integrity. It has been reported that p120ctn regulates the function of vascular endothelium as an innate immune factor. P120ctn phosphorylation will increase transcription of inflammatory factors, as NF-ΚΒ, Rho and MPO, and induce the inflammatory in vascular endothelium. Inflammatory has been showed to play critical role in the formation of intracranial aneurysm, however, the regulation of inflammatory in endothelial cells is not well clear yet. In this study, we are about to explore the relationship between inflammatory and p120ctn phosphorylation in endothelial cells and try to test the hypothesis that NF-ΚΒ,Rho and MPO signal initiated by p120ctn phosphorylation is involved in the formation of experimental intracranial aneurysm .