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中华神经创伤外科电子杂志 ›› 2024, Vol. 10 ›› Issue (01) : 48 -54. doi: 10.3877/cma.j.issn.2095-9141.2024.01.008

综述

中枢神经系统AQP4的调节机制研究进展
程亚飞1, 郭航2,†()   
  1. 1. 030001　太原，山西医科大学麻醉学院
    2. 100010　北京，解放军总医院第七医学中心麻醉科
  • 收稿日期:2023-02-02 出版日期:2024-02-15
  • 通信作者: 郭航

Research progress on the regulatory mechanism of AQP4 in central nervous system

Yafei Cheng1, Hang Guo2,†()   

  1. 1. College of Anesthesiology, Shanxi Medical University, Taiyuan 030001, China
    2. Department of Anesthesiology, the 7th Medical Center, PLA General Hospital, Beijing 100010, China
  • Received:2023-02-02 Published:2024-02-15
  • Corresponding author: Hang Guo
  • Supported by:
    National Natural Science Foundation of China(82101427)
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程亚飞, 郭航. 中枢神经系统AQP4的调节机制研究进展[J]. 中华神经创伤外科电子杂志, 2024, 10(01): 48-54.

Yafei Cheng, Hang Guo. Research progress on the regulatory mechanism of AQP4 in central nervous system[J]. Chinese Journal of Neurotraumatic Surgery(Electronic Edition), 2024, 10(01): 48-54.

水通道蛋白-4（AQP4）是哺乳动物中枢神经系统最主要的水通道，在脑微血管周围的星形胶质细胞足突密集表达，参与调节脑内水平衡、K+离子缓冲空间、神经胶质瘢痕形成、淋巴清除、神经元兴奋性、突触可塑性和行为等诸多生物学过程。目前研究发现，AQP4与缺血性脑损伤、癫痫、抑郁和阿尔兹海默病等中枢神经系统疾病有关，因此靶向调节AQP4有望成为中枢神经系统疾病的新型治疗策略。本文围绕AQP4的内源性调节方式和调节剂，以及AQP4的调控在中枢神经疾病中的最新进展进行综述，旨在为靶向调节AQP4的临床转化提供理论基础。

关键词: 水通道蛋白-4, 中枢神经系统疾病, 星形胶质细胞

Aquaporin 4 (AQP4) is the main water channel in the mammalian central nervous system (CNS), around the astrocyte cell foot process dense expression, involved in regulating the brain water balance, K+ buffer space, glial scar formation, lymphatic clearance, neuronal excitability, synaptic plasticity and behavior, and many other biological processes. Current findings, AQP4 is associated with CNS diseases such as ischemic brain injury, epilepsy, depression and Alzheimer's disease, so targeted modulation of AQP4 is expected to be a novel therapeutic strategy for CNS diseases. This article reviews the endogenous regulation mode and regulators of AQP4 and the recent progress of AQP4 regulation in CNS disorders, aiming to provide a rationale for the clinical translation of targeted regulation of AQP4.

Key words: Aquaporin 4, Central nervous system disease, Astrocyte
图1 AQP4的跨膜结构及NAP折叠结构A：跨膜结构；B：NAP折叠结构
Fig.1 Transmembrane structure and NAP folding structure of AQP4
表1 AQP4存在的磷酸化位点及其作用
Tab.1 Phosphorylation sites of AQP4 and their effects
蛋白激酶 磷酸化位点 主要作用 动物模型与细胞
PKA S276[20] AQP4内化增加 AQP4cDNA转染的人胃细胞
    促进AQP4易位到质膜，表达水平下调 AQP4cDNA转染的HEK293细胞、大鼠原代星形胶质细胞
PKC S180[18,21] AQP4内化增加 大鼠模型、非洲爪蟾卵母细胞、人胶质瘤细胞
    AQP4位置未变化，降低AQP4的透水性，具有潜在门控特性 猪肾上皮细胞细胞
PKG S111    
CKⅡ S276、S285、T289、S316 促进AQP4易位到质膜 小鼠原代星形胶质细胞
CaMKⅡ S111（间接）[19] 提高AQP4的透水性，具有潜在门控特性（争议） 大鼠星形胶质细胞
未知 S285、S315、S316、S321、S322[20] 对AQP4的运输和通道门控均无影响 非洲爪蟾卵母细胞
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