水通道蛋白-4的激活可促进胶质淋巴系统功能及脑出血后血肿清除  

Aquaporin-4 activation facilitates glymphatic system function and hematoma clearance post-intracerebral hemorrhage

作　　者：Wenchao Chen Chuntian Liang Shasha Peng Shuangjin Bao Fang Xue Xia Lian Yinghong Liu GaiqingWang 王晶(编译) 

机构地区：[1]Department of Neurology,Second Hospital of Shanxi Medical University,Shanxi Medical University,Taiyuan,Shanxi,China. [2]Department of Neurology,Sanya Central Hospital(Hainan Third People's Hospital),Hainan Medical University,Sanya,Hainan,China. [3]Department of Pharmacology,School of Basical Medical Sciences,Shanxi Medical University,Taiyuan,China. [4]Department of Pharmacy,Sanya Central Hospital(Hainan Third People's Hospital),Hainan Medical University,Sanya,China. [5]Department of Pathology and Pathophysiology,Basic Medical College,Shanxi Medical University,Taiyuan,China. [6]Department of Pathology,West China Fourth Hospital,Chengdu,China [7]不详

出　　处：《神经损伤与功能重建》2024年第11期F0003-F0003,共1页Neural Injury and Functional Reconstruction

摘　　要：有效清除血肿对于改善脑出血(ICH)患者的临床结局至关重要。由水通道蛋白-4(AQP4)促进的胶质淋巴系统在脑脊液(CSF)流入和代谢废物清除方面发挥关键作用。本研究探讨胶质淋巴系统在脑出血病理中的作用,重点关注AQP4。本研究建立了胶原酶诱导的脑出血模型,并通过米非司酮作为激动剂、TGN-020作为抑制剂以及Aqp4基因敲除来调控AQP4表达。采用荧光示踪和多模态磁共振成像(MRI)观察胶质淋巴系统功能、血肿和水肿体积。使用改良Garcia量表(modified GarciaScale)进行神经功能缺损评分。采用RT-qPCR和Westernblotting量化AQP4表达,并利用免疫荧光探索其细胞定位。检查脑组织切片中的神经元形态、退行性改变和铁沉积。脑出血后第3天,AQP4激动剂组表现出AQP4蛋白表达增加和血管周围极化增强、血红蛋白水平降低以及铁沉积减少。抑制组则呈现相反的趋势。AQP4的激活改善了胶质淋巴系统功能,导致分布范围更广、神经功能改善和血肿减少。AQP4的药理学抑制和基因敲除具有相反的效果。由AQP4促进的胶质淋巴系统在脑出血后的血肿清除中发挥关键作用。上调AQP4可改善胶质淋巴系统功能,促进血肿清除,并促进脑组织恢复。Efficient clearance of hematomas is crucial for improving clinical outcomes in patients with intracerebral hemorrhage(ICH).The glymphatic system,facilitated by aquaporin-4(AQP4),plays a crucial role in cerebrospinal fluid(CSF)entry and metabolic waste clearance.This study examined the role of the glymphatic system in ICH pa-thology,with a focus on AQP4.Collagenase-induced ICH models were established,with AQP4 expression regulated through mifepristone as an agonist,TGN-020 as an inhibitor,and Aqp4 gene knockout.Fluorescence tracing and multimodal magnetic resonance imaging(MRI)were employed to observe glymphatic system functionality,hemato-ma,and edema volumes.Neurological deficit scoring was performed using the modified Garcia Scale.AQP4 expres-sion was quantified using RT-qPCR and Western blotting,and cellular localization was explored using immunofluo-rescence.The brain tissue sections were examined for neuronal morphology,degenerative changes,and iron deposi-tion.Three days post-ICH,the AQP4 agonist group showed increased AQP4 protein expression and perivascular po-larization,decreased hemoglobin levels,and reduced iron deposition.Conversely,the inhibition group exhibited con-trasting trends.AQP4 activation improved glymphatic system function,leading to a wider distribution,improved neurological function,and reduced hematoma.Pharmacological inhibition and genetic knockout of AQP4 have op-posing effects.The glymphatic system,facilitated by AQP4,plays a crucial role in hematoma clearance following ce-rebral hemorrhage.Upregulation of AQP4 improves glymphatic system function,facilitates hematoma clearance,and promotes brain tissue recovery.

关 键 词：水通道蛋白-4(AQP4) 胶质淋巴系统 血肿清除 脑出血 

分 类 号：R741[医药卫生—神经病学与精神病学] R741.02[医药卫生—临床医学]