脉络丛上皮细胞炎症反应引起TLR4/NF-κB/NKCC1通路激活在交通性脑积水发生中的作用及机制

交通性脑积水是以脑脊液分泌和吸收障碍为特征的疾病，发病率高，可继发于多种神经系统疾患，手术并发症多，治疗效果差。相比治疗脑积水，预防脑积水的形成具有更高的研究潜力。在脑积水发生早期和中期，炎症反应和脑脊液分泌异常关系密切。本项目前期实验结果证实，在炎症反应条件下，脉络丛上皮细胞分泌增多，引发炎症性脑积水，这一过程可能是由于TLR4/NF-κB信号通路异常激活，pNKCC1-pSPRK复合体在脉络从上皮细胞胞膜上表达增强，从而强化脉络丛上皮细胞NKCC1结合和磷酸化过程，导致下游因子水通道蛋白1激活，引起脑脊液分泌增多。本项目在前期工作基础上提出假说，通过脉络丛上皮细胞培养和脑积水动物模型建立，并在体内和体外分别调控该信号通路上下游关键蛋白，探究并阐述炎症反应通过TLR4/NF-κB信号通路激活NKCC1及AQP1引起脑积水的分子机制，探究治疗脑积水的新方向。

Hydrocephalus is characterized by secretion, circulation and absorption disorder of cerebrospinal fluid (CSF) with high morbidity, high complication rate and poor treatment effect. Compared to treating patients who already developed hydrocephalus,the prevention of hydrocephalus represent higher research potential. In the Early and middle stages of hydrocephalus, the relationship between inflammation and abnormal secretion of CSF by choroid plexus epithelium (CPE) received more attention recently. Under inflammatory conditions, TLR4-dependent activation,Ste20-type stress kinase SPAK and pNa+-K+-2Cl cotransporter (pNKCC1)co-transporter expression boosting and NKCC1 binding and phosphorylation in choroid plexus epithelial cells enhanced. It will result in the AQP1 activation abnormal secretion of CSF. Our hypothesis is based on our previous work through the CPE cultivation and hydrocephalus model establishment to investigate the mechanism of the inflammation response activating NKCC1 and AQP1 by TLR4/NF-κB/NKCC1 signal pathway and explore the therapeutic effect of regulating CPE hyper-secretion. It will provide new idea of the pathogenesis and treatment of hydrocephalus.