脑血管内皮细胞与神经元之间的相互作用可能在血管性认知功能障碍中发挥重要作用。结合文献和前期研究，我们得出假说：受损脑血管内皮细胞可以通过释放凋亡外泌体（AEVs）对神经元突触兴奋性发生影响。AEVs作为特殊的细胞外囊泡，其特异性表面标记S1P与神经元S1PR的相互作用，介导了AEVs被神经元所吞噬。从而将内皮细胞来源的AEVs中携带的高表达LncRNA NEAT1带入受体神经元。而在神经元内，NEAT1通过介导钾离子通道蛋白KCNE1的细胞内转位过程，增强了钾离子通道Kv7/KCNQ功能，钾离子M电流增强，神经元动作电位后fAHP延长，神经元兴奋性下降。为验证此假说，拟采用多种体内体外模型结合分子生物学、电生理等技术，探索内皮细胞来源AEVs通过LncRNA NEAT1介导神经元突触兴奋性的具体分子机制。从凋亡外泌体介导内皮细胞和神经元相互作用这一新视角阐释血管性认知功能障碍的发病机制。

The interaction between cerebrovascular endothelial cells and neurons may play an important role in vascular cognitive impairment. Combined with literature and our previous results, we hypothesized that apoptotic cerebrovascular endothelial cells could influence neuronal intrinsic excitability and synaptic responses by releasing apoptotic exosome-like vesicles (AEVs). As a special extracellular vesicle, AEVs have a unique marker protein S1P. The interaction between S1P and its receptor S1PR which localized on neurons mediated the neuronal uptake of endothelial cell-derived AEVs. Thus, the LncRNA NEAT1 in the endothelial cell-derived AEVs was taken by receptor neurons. In neurons, NEAT1 mediates the intracellular translocation of potassium channel interacting protein KCNE1, enhances the function of potassium channel Kv7/KCNQ, and activate the M-current. NEAT1 modulates the excitability and synaptic transmission of neurons by increase first inter-spike interval (ISI), spike onset latency and prolongs fast afterhyperpolarization (fAHP). To verify this hypothesis, several in vivo and in vitro models combined with molecular biology, electrophysiology and other techniques were used to explore the specific molecular mechanism of neuronal synaptic excitability mediated by endothelial cell-derived AEVs through LncRNA NEAT1. The pathogenesis of vascular cognitive impairment is explained from the new perspective of apoptotic exosomes mediating the interaction between endothelial cells and neurons.