Inhibition of the immunoproteasome LMP_(2) ameliorates ischemia/hypoxia-induced blood–brain barrier injury through the Wnt/β-catenin signalling pathway

作     者：Xing-Yong Chen Shao-Fen Wan Nan-Nan Yao Ze-Jing Lin Yan-Guang Mao Xiao-Hua Yu Yin-Zhou Wang Xing?Yong Chen;Shao?Fen Wan;Nan?Nan Yao;Ze?Jing Lin;Yan?Guang Mao;Xiao?Hua Yu;Yin?Zhou Wang

作者机构：Department of NeurologyFujian Provincial HospitalShengli Clinical Medical College of Fujian Medical UniversityNo.134DongjieGulou DistrictFuzhou 350001China Fujian Academy of Medical ScienceFuzhou 350o01China Key Testing Laboratory of Fujian ProvinceFuzhou 350001China. 

出 版 物：《Military Medical Research》 (军事医学研究（英文版）)

年 卷 期：2022年第9卷第4期

页      面：404-418页

核心收录：

学科分类：1001[医学-基础医学(可授医学、理学学位)] 100102[医学-免疫学] 10[医学] 

基　　金：supported by the National Natural Science Foundation of China(81771250) the Natural Science Foundation of Fujian Province,China(2020J011059,2020R1011004) the Joint Funds for the Innovation of Science and Technology of Fujian Province,China(2017Y9065) the High-level hospital foster grants from Fujian Provincial Hospital,Fujian Province,China(2020HSJJ07) 

主　　题：Immunoproteasome Blood–brain barrier Wnt/β-catenin pathway Oxygen–glucose deprivation/reperfusion Cerebral ischemia 

摘      要：Background:Disruption of the blood–brain barrier(BBB)after a stroke can lead to brain injury and neurological *** work confirmed the involvement of the immunoproteasome subunit of low molecular mass peptide 2(LMP2)in the pathophysiology of ischemia ***,the relationship between the immunoproteasome LMP2 and the BBB remains ***:Adult male Sprague–Dawley rats were subjected to transient middle cerebral artery occlusion/reperfusion(MCAO/R).Three days before MCAO,the rats were treated with lentivirus-mediated LMP2 shRNA preparations by stereotactical injection into the ipsilateral hemispheric *** rat brain microvascular endothelial cell(RBMVEC)line was exposed to oxygen–glucose deprivation/reperfusion(OGD/R)to mimic ischemic conditions in *** RNA interference-mediated knockdown of LMP2 orβ-catenin was analysed in vivo and in *** of the quantity of extravasated Evans blue(EB)and cerebral fluorescent angiography were performed to evaluate the integrity of the *** and Western blotting were employed to detect the expression of target *** migration was evaluated using a scratch migration *** results of immunofluorescence,Western blotting and cell migration were quantified using the software ImageJ(Version 1.53).Parametric data from different groups were compared using one-way ANOVA followed by the least significant difference(LSD)***:Cerebral ischemia led to lower levels of structural components of the BBB such as tight junction proteins[occludin,claudin-1 and zonula occludens(ZO-1)]in the MCAO/R group compared with the sham group(P0.001).However,inhibition of the immunoproteasome LMP2 restored the expression of these proteins,resulting in higher levels of occludin,claudin-1 and ZO-1 in the LMP2-shRNA group compared with the control-shRNA group(P0.001).In addition,inhibition of the immunoproteasome LMP2 contributed to higher microvascular density and decreased BBB perm