具有水转运功能的水通道蛋白-4（AQP4）对脑膜炎脑水肿的发生具有重要作用。我们前期在幼鼠脑膜炎脑内发现：AQP4从星形胶质细胞膜进入细胞内的内化过程参与了脑膜炎脑水肿的发生发展。因此探讨AQP4内化的发生机制并干预其过程，有望为脑水肿的治疗开辟新途径。研究表明，炎症激活的NF-κB可上调基质金属蛋白酶(MMPs)表达；另有研究发现MMPs可促进dystroglycan（DG）和laminin蛋白的降解；而DG和laminin等是使AQP4锚定在细胞膜上的重要分子。因此，在脑膜炎脑水肿中，AQP4内化的发生可能与NF-κB活化导致的AQP4锚定因素破坏相关。本课题将以“炎症刺激—NF-κB激活—MMPs表达上调—AQP4锚定因素破坏—AQP4内化”为轴线，研究在脑膜炎脑水肿中NF-κB激活对AQP4内化的影响及机制。本课题有望阐明AQP4内化的分子机制，为开发治疗脑水肿新药提供实验依据。

Aquaporin-4(AQP4) plays an important role in the development of brain edema induced by meningitis. In the previous study, we have found that AQP4 was internalized from the astrocytes membrane to the intracellular endosome in the brain with meningitis and that the internalization of AQP4 was involved in the development of brain edema. Therefore, elucidating the mechanism of AQP4 internalization and taking corresponding measures to regulate the process of AQP4 internalization are expected to open up new ways for the treatment of brain edema. The results of some researches demonstrated that inflammation stimulation can make the activation of NF-κB, which serves as a pivotal transcription factor upregulating the expression of matrix metalloproteinases (MMPs). Other literatures showed that MMPs can cleave dystroglycan and laminin, which are important factors for AQP4 anchored at proper membrane domain. Based on above research foundings, we propose that the degrading of AQP4 anchoring factors caused by activation of NF-κB may be involved in the internalization of AQP4. In this study, we will study the effect and mechanism of NF-κB activation on AQP4 internalization in the brain with meningitis following the axial line of ‘inflammatory stimulations—NF-κB activation—upregulation of MMPs—degrading of AQP4 anchoring factors—AQP4 internalization’. The results of this study can supply an experimental basis for clarifying the mechanism of AQP4 internalization and developing therapeutic drugs for the treatment of brain edema.