突触后致密蛋白95（PSD95）在脑缺血损伤中发挥重要作用，但其作用机制有待进一步深入解析。本课题组率先发现PSD95与Mas存在相互作用，PSD95能增加Mas的细胞膜定位；同时，最新研究结果提示PSD95可能通过抑制Mas受体的内化，进而减弱Mas介导的信号通路，从而抑制Ang-(1-7)-Mas介导的脑缺血保护作用。本项目将利用可直接破坏PSD95与Mas作用的穿膜肽Tat-MAS9C，结合PSD95表达改变（慢病毒过表达和siRNA干扰），进一步研究PSD95对Ang-(1-7)处理的氧糖剥夺（OGD）神经元中Mas细胞膜定位的影响；在大鼠大脑中动脉梗塞（MCAO）模型和OGD神经元模型中研究PSD95对Ang-(1-7)-Mas介导的脑缺血保护作用及相关的关键信号通路（NF-κB、AKT）的调控。以揭示PSD95调控脑缺血损伤的新机制，为脑缺血相关疾病的治疗提供新思路。

Post synaptic density protein 95 (PSD95) play an important role in regulating cerebral ischemia. But its regulatory mechanisms are not fully understood. We reported for the first time that PSD95 can interact strongly with Mas, and PSD95 can increase the Mas localization in cell membrane. At the same time, the latest research results suggest PSD95 may reduce the Mas-mediated signaling pathways by inhibiting the internalization of Mas receptor, thereby inhibiting the Ang-(1-7) -Mas-mediated cerebral ischemia protection. This project will use the new peptide Tat - MAS9C to directly destroy the interaction of PSD95 and Mas. Tat - MAS9C treatment and PSD95 expression change (lentivirus overexpression and siRNA interference) will be used to further study the effects of PSD95 on Mas membrane positioning in oxygen and glucose deprivation (OGD) neurons treated by Ang - (1-7). In addition, the rat middle cerebral artery occlusion (MCAO) model and OGD model were used to study the regulatory effects of PSD95 on Ang-(1-7) -Mas-mediated cerebral ischemia protection and the related key signaling pathways (NF-κB、AKT). The above studies can reveal the new mechanism of PSD95 to regulate cerebral ischemia injury, and provide new ideas for the treatment of cerebral ischemia related diseases.