血管性痴呆(VD)的治疗是业界攻克的难点，中医药确有疗效，但作用机制尚不明晰。国外最新研究发现网格蛋白Clathrin是VD患者脑内降低最显著的突触相关蛋白，其介导的神经元N甲基D天冬氨酸（NMDA）受体胞吞减少使兴奋性氨基酸毒性大大增强，最终导致神经元凋亡。在“正虚毒损络阻”理论指导下的参知健脑方，已完成临床前研究，初步发现其对VD大鼠模型的神经元损伤有修复作用。本课题拟分别建立缺血再灌注VD大鼠模型和体外培养谷氨酸损伤海马神经元VD细胞模型，采用行为学、免疫学和分子生物学技术，检测VD大鼠模型脑组织以及细胞模型中clathrin以及其标记物Rab5b和NMDA等表达分布变化，并以NMDA 受体拮抗剂美金刚作为对照组，从整体、组织、细胞和蛋白分子水平，验证参知健脑方对clathrin介导的NMDA受体胞吞过程和不同时点动态变化有调节作用的假设，为中医药治疗VD提供崭新科学依据。

The pathogenesis and treatment of vascular dementia (VD) is the difficulty and focus of industry. Chinese medicine has effect of anti-aging and Vascular sclerosis, but the mechanism is not clear. The latest foreign study found that clathrin was the most significant reduced synapse-associated protein in VD patients brain, which mediated N-methyl-D-aspartic acid (NMDA) receptor endocytosis. The over load of NMDA receptor could increase the excitatory amino acid toxicity of glutamate, ultimately leading to neuronal apoptosis. By the support of National Major New Drug Development Program of Ministry of Science the efficacy study has already Verified Shen Zhi Jian Nao formula has the effect of repairing of neuron injury rat model of VD, which was under the theory of “ZhengXuDuSun”. This research will establish ischemia and reperfusion VD rats model and glutamate damaged hippocampal neurons VD cell model, using NMDA receptor antagonist memantine as a control group, using immunocytochemistry, immunohistochemistry, RT-PCR and western blotting experiments technique to detect the change of NMDA-NR1, clathrin and its markers Rab5b in rat brain tissue and cell models. To study on the influence of Shen Zhi Jian Nao formula on clathrin-mediated NMDA endocytosis and its dynamic changes at different time points. Provide scientific evidence of a new target for medical treatment of VD.