The Regulatory Role and Mechanism of Circadian Rhythm in Hemoglobin Co-cultured Neurovascular Unit  

作　　者：Fang Xue Wenchao Chen Xia Lian Guanghui He Jingyuan Tian Yinghong Liu Gaiqing Wang 

机构地区：[1]Department of Neurology,The Second Clinical School of Medicine,Shanxi Medical University,Taiyuan 030002,Shanxi,China [2]The Second Clinical School of Medicine,Shanxi Medical University,Taiyuan 030002,Shanxi,China [3]Department of Clinical lab,The First People’s Hospital of Zhaotong,Zhaotong 657000,Yunnan,China [4]Department of Neurology,Sanya Central Hospital(Hainan Third People’s Hospital)Hainan Medical University,Sanya 57200,Hainan,China

出　　处：《Biomedical and Environmental Sciences》2024年第7期726-738,共13页生物医学与环境科学（英文版）

基　　金：supported by the National Natural Science Foundation of China(No.82160237);the Key Research and Development Program in Hainan Province(No.ZDYF2023SHFZ104);Natural Science Foundation of Hainan Province(No.822MS210).

摘　　要：Objective Intracranial hemorrhage(ICH),the second most common subtype of stroke,exacerbates the disruption of the blood-brain barrier(BBB),leading to vasogenic edema,plasma protein extravasation,and infiltration of neurotoxic substances.The clearance capacity of the brain plays a crucial role in maintaining BBB homeostasis and facilitating patient recovery after hemorrhage.This study aimed to investigate the effect of circadian rhythms on BBB function,neuronal damage,and clearance capabilities.Methods The transwell model and hemoglobin were co-cultured to simulate the BBB environment after ICH.After intervention with different light groups,neuronal apoptosis was determined,glial phagocytosis was analyzed,the expression of endogenous clearing-related proteins aquaporin 4(AQP4)and low-density lipoprotein receptor-related protein 1(LRP1)was detected by western blotting and immunofluorescence dual standard method,and the expression of the tight junction protein occludin and melatonin receptor 1A(MTNR1A)was quantitatively analyzed.Results Circadian rhythms play a key role in maintaining the integrity of the BBB,reducing oxidative stress-induced neuronal damage,and improving microglial phagocytosis.Meanwhile,the expression of occludin and MTNR1A in neurovascular unit(NVU)co-cultured with hemoglobin improved the expression of AQP4 and LRP1,the key proteins in the NVU's endogenous brain clearance system.Conclusion Circadian rhythm(alternating black and white light)protects the NVU BBB function after ICH,promotes the expression of proteins related to the clearance of the hematoma,provides new evidence for the clinical treatment of patients recovering from ICH,and improves the circadian rhythm to promote brain metabolism and hematoma clearance.

关 键 词：Blood-brain barrier Circadian rhythm Neurovascular unit Melatonin receptor 1A AQUAPORIN-4 

分 类 号：R338[医药卫生—人体生理学]