血管性痴呆（Vascular Dementia，VD）的发生与神经元缺血缺氧损伤后细胞异常折叠蛋白增多、受损细胞器蓄积、“内生浊毒”，最终诱发细胞凋亡有关；细胞内自噬-溶酶体途径激活、降解聚集的有害物质，则合“泄毒活血”之理。本课题组前期针对VD酿毒损髓的病机特点，以泄毒活血化痰为治疗方法，使用脑络通方临床治疗VD 取得了较好疗效，预实验发现这种保护作用与自噬相关，但其具体作用机制尚不明确；因此，在前期工作基础上，本课题组提出“脑络通方抗VD的机制可能与其促进自噬体及时降解，发挥泄浊排毒之功效有关”。本项目拟应用双侧颈总动脉结扎导致VD的动物模型，以及氧糖剥夺的细胞模型，通过检测自噬-溶酶体途径关键蛋白，从体外实验和体内实验研究脑络通方是否通过自噬ERK2/TFEB/LAMP-1通路，增强自噬体降解、泄浊排毒，维持细胞内环境稳态，发挥神经保护作用。

Vascular Dementia(VD) is closely related to the increase of cell misfolded protein after the neuron under ischemia-hypoxia injury, accumulation of damaged cell organelle and “inner-produced turbid toxins” ,which will finally cause cell apoptosis.It is in accordance with the idea of “Toxicant Elimination and activating blood circulation” that the autophagy-lysosomal pathway will be activated,and degrade the harmful substances. In the early stage, the research group focused on pathological characteristics of VD brewing toxin and harming marrow and took disinfection, invigorating the circulation of blood and expelling phlegm as the therapeutic method to treat VD by using Naoluotong prescription, the clinical effect proved to be satisfactory.It turned out such protection is related to autophagy, while the specific mechanism is not clear. Therefore, based on the preliminary work, the research team proposed the idea that “mechanism of Naoluotong granule resisting VD may be related to its promoting the timely degradation of autophagosome and effect of turbidity and Toxicant elimination”. The project plans to apply the animal model of VD by ligating bilateral carotid arteries and oxgen-glucose deprivation-induced cell model, by testing key protein of autophagy-lysosomal pathway to study from in-virto experiment and in-vivo experiment about whether Naoluotong granule can enhance autophagy degradation, eliminate turbidity and toxicant, maintain the stable condition in cells and exert neuro-protective effect through autophagy ERK2/TFEB/LAMP-1 access.