Activation of the wnt/β-catenin/CYP1B1 pathway alleviates oxidative stress and protects the blood-brain barrier under cerebral ischemia/reperfusion conditions  

作　　者：Xingyong Chen Nannan Yao Yanguang Mao Dongyun Xiao Yiyi Huang Xu Zhang Yinzhou Wang 

机构地区：[1]Department of Neurology,Fujian Provincial Hospital,Shengli Clinical Medical College of Fujian Medical University,Fuzhou,Fujian Province,China [2]Department of Neurology,Cangzhou Central Hospital,Cangzhou,Hebei Province,China [3]Fujian Academy of Medical Science,Fuzhou,Fujian Province,China [4]Key Testing Laboratory of Fujian Province,Fuzhou,Fujian Province,China

出　　处：《Neural Regeneration Research》2024年第7期1541-1547,共7页中国神经再生研究（英文版）

基　　金：supported by the National Natural Science Foundation of China,No.81771250(to XC);the Natural Science Foundation of Fujian Province,Nos.2020J011059(to XC),2020R1011004(to YW),2021J01374(to XZ);Medical Innovation Project of Fujian Province,No.2021 CXB002(to XC);Fujian Research and Training Grants for Young and Middle-aged Leaders in Healthcare(to XC)。

摘　　要：Accumulating evidence suggests that oxidative stress and the Wnt/β-catenin pathway participate in stroke-induced disruption of the blood-brain barrier.However,the potential links between them following ischemic stroke remain largely unknown.The present study found that cerebral ischemia leads to oxidative stress and repression of the Wnt/β-catenin pathway.Meanwhile,Wnt/β-catenin pathway activation by the pharmacological inhibito r,TWS119,relieved oxidative stress,increased the levels of cytochrome P4501B1(CYP1B1)and tight junction-associated proteins(zonula occludens-1[ZO-1],occludin and claudin-5),as well as brain microvascular density in cerebral ischemia rats.Moreove r,rat brain microvascular endothelial cells that underwent oxygen glucose deprivation/reoxygenation displayed intense oxidative stress,suppression of the Wnt/β-catenin pathway,aggravated cell apoptosis,downregulated CYP1B1and tight junction protein levels,and inhibited cell prolife ration and migration.Overexpression ofβ-catenin or knockdown ofβ-catenin and CYP1B1 genes in rat brain mic rovascular endothelial cells at least partly ameliorated or exacerbated these effects,respectively.In addition,small interfering RNA-mediatedβ-catenin silencing decreased CYP1B1 expression,whereas CYP1B1 knoc kdown did not change the levels of glycogen synthase kinase 3β,Wnt-3a,andβ-catenin proteins in rat brain microvascular endothelial cells after oxygen glucose deprivatio n/reoxygenation.Thus,the data suggest that CYP1B1 can be regulated by Wnt/β-catenin signaling,and activation of the Wnt/β-catenin/CYP1B1 pathway contributes to alleviation of oxidative stress,increased tight junction levels,and protection of the blood-brain barrier against ischemia/hypoxia-induced injury.

关 键 词：blood-brain barrier CYP1B1 oxidative stress oxygen glucose deprivation/reoxygenation tight junction vascular endothelial cells Wnt/β-catenin pathway β-catenin 

分 类 号：R743.3[医药卫生—神经病学与精神病学]