VEGF信号通路介导血脑屏障损伤在视神经脊髓炎发病启动机制中作用的研究

视神经脊髓炎相关性视神经炎（NMO-ON）是导致视功能不可逆性严重损害的一种视神经炎，在亚洲复发性视神经炎中其发病率高达60%。主要病理机制是血脑屏障（BBB）破坏后，外周血致病性水通道蛋白4 抗体进入中枢神经系统（CNS），引起星形胶质细胞病变，继发神经轴突坏死。其中BBB损伤是发病过程中的关键因素。然而，NMO-ON发病过程中BBB损伤分子机制不明。新近研究发现血管内皮生长因子（VEGF） 信号通路在CNS炎性疾病血管通透性改变中发挥重要作用，我们提出假设，VEGF信号通路是NMO-ON BBB损伤机制中的关键效应器。本研究拟建立NMO-ON动物模型，通过调控VEGF信号通路，采用分子生物学、影像学及电生理等方法，观察模型表型，BBB损伤及VEGF通路表达情况，得到VEGF信号通路在NMO-ON BBB损伤中效应器作用的直接证据，进一步阐明NMO-ON的发病机制，为其治疗提供新的靶点。

Neuromyelitis Optica (NMO) related Optic Neuritis(NMO-ON) is a devastating disease that cause irreversible severe visual damage. NMO-ON had an extremely high prevalence of 60% in Asian relapse ON. Its main pathological mechanism is blood-brain-barrier (BBB) damage, leading to infuse of Aquasporine 4 Antibody into central nerve system(CNS), causing astrocyte damage, leading to secondary demyelination and axon damage. Therefore, BBB damage is considered as the key procedure in NMO. Recent research discovered that VEGF signal pathway plays an.important role in BBB damage in CNS inflammation and could even be the most important effector. However, there was no research about the effect of VEGF signal pathway in NMO-ON. In this research we planed to establish a NMO-ON animal model to clarify the BBB damage mediated by VEGF signal pathway, VEGFA-VEGFR2-eNOS, by molecular biology, radiology and electrophysiology methods. This research might.provide direct evidence of the effector role of VEGF signal pathway in BBB damage during the initiation of NMO-ON, which might be a novel treatment target for NMO-ON.