血管性痴呆（VD）是目前唯一可防治的痴呆类型。海马神经元转归是VD有效防治的关键，然其核心机制如何？目前尚不清楚。线粒体自噬能维持NVU整体功能并对神经元转归产生影响。课题组前期在多项各级课题的支持下发现：VD的发生伴随海马线粒体自噬被抑制及NRs表达异常；NRs与海马NVU整体功能、神经突触可塑性密切相关。而NRs可通过PINK1/parkin信号通路调节线粒体自噬。本项目拟采用透射电镜、高内涵、膜片钳等技术，结合激动剂、阻断剂、基因沉默及过表达等方式，从在体、离体两方面揭示“VD状态下，NRs通过PINK1/parkin信号通路调节线粒体自噬，使海马NVU形态与功能发生改变，进而对其神经元转归产生影响”的分子机制；并用“滋肾填精、活血通络”立法方药干预，反证“肾精阴虚、瘀阻脑络”中医病机。该研究将为VD认知功能恢复提供新的理论依据与防治策略。

Vascular dementia (VD) is the only type of dementia that can be prevented and treated. Outcomes of neurons in hippocampus are considered critical for the rehabilitation of cognitive function, but the exact mechanism is still remained unclear. Mitophagy can maintain the function of neurovascular unit(NVU) and affect the outcomes of neurons. With the support of several National Natural Science Foundation of China and provincial items, we found that: I. The damage of hippocampal neurovascular unit induced by NRs was closely related to the impairment of learning and memory; II. VD is always accompanied by the abnormal expression of NRs, the alteration of morphology in Hippocampal NVU, and the changes of structure and quantity in mitochondrion. Importantly, NRs is closely associated with the mitophagy induced by PINK1/parkin. The project aims to use TEM, FCM, Luminex technology, inhibitor, activator, gene knockout, and gene silence, revealing the mechanism of neuronal outcomes mediated by the mitophagy induced by PINK1/parkin and through the regulation of NRs, which affect the morphology and function of hippocampal NVU in vivo and in vitro. The theory of “invigorating the kidney and enriching essence, promoting blood circulation” is applied to disproof the pathology (Kidney essence deficiency and blood stasis blocking brain) of VD, which providing new ideas and targets for the prevention and treatment of VD.