EGCG通过调控LXRβ-RXRα-ABCA1通路抑制N2a/APP695swe细胞内Aβ生成的机制研究  

Mechanism of epigallocatechin-3-gallate for inhibiting Aβgeneration in N2a/APP695swe cells via regulation of LXRβ-RXRα-ABCA1 pathway

作　　者：王谑菲 王慧 杨甫兰 杨娜 杨柳[1] WANG Xuefei;WANG Hui;YANG Fulan;YANG Na;YANG Liu(Department of Neurology,Chongqing Municipal Emergence Medical Center/Affiliated Central Hopital,Chongqing University,Chongqing 400010,China)

机构地区：[1]重庆市急救医疗中心/重庆大学附属中心医院神经内科,重庆400010

出　　处：《重庆医学》2025年第1期12-17,共6页Chongqing Medical Journal

基　　金：重庆市科卫联合医学科研项目(2023MSXM101);急诊医学重庆市重点实验室人才创新发展联合基金项目(2024RCCX08)。

摘　　要：目的研究表没食子儿茶素-3-没食子酸酯(EGCG)在稳定转染Swedish家族型突变的人淀粉样前体蛋白(APP)695细胞(N2a/APP695swe)β淀粉样蛋白(Aβ)生成中的影响及机制。方法将N2a/APP695swe行体外培养,EGCG[或联合肝X受体β(LXRβ)拮抗剂GSK2033]按照不同浓度分别作用于细胞,并设置二甲基亚砜(DMSO)组和野生型小鼠神经瘤母细胞(N2a/wt)组。采用MTT法检测细胞存活率,ELISA检测Aβ42水平,Western blot检测LXRβ、类视黄醇X受体α(RXRα)、ATP结合盒转运子A1(ABCA1)、窖蛋白-1(caveolin-1)和β-分泌酶1(BACE1)蛋白表达。结果20、40μmol/L EGCG组细胞存活率、Aβ42水平较其他组改善明显(P<0.05),且呈浓度依赖性(P<0.05)。20μmol/L EGCG作用后,LXRβ、RXRα和ABCA1蛋白表达升高,aveolin-1、BACE1蛋白表达明显降低,差异有统计学意义(P<0.05);联合GSK2033处理细胞后,LXRβ、RXRα和ABCA1蛋白表达明显降低,caveolin-1、BACE1蛋白表达明显升高(P<0.05)。结论N2a/APP695swe细胞内Aβ42的生成能被EGCG抑制从而抑制细胞的增殖,其机制可能与EGCG激活LXRβ-RXRα-ABCA1通路进而抑制caveolin-1和BACE1表达有关。Objective To study its effect and mechanism of epigallocatechin-3-gallate(EGCG)on the generation of Aβ42 in N2a/APP695swe cells.Methods The N2a/APP695swe cells were cultured in vitro and treated with different concentrations of EGCG(or in combination with LXRβantagonist GSK2033).The DMSO group and wild type N2a/wt group were set.The cellular survival rate was detected by the MTT assay;ELISA was used to detect the Aβ42 level;Western blot was used to detect the expression levels of LXRβ,RXRα,ABCA1,caveolin-1 and BACE1 proteins.Results The cellular survival rate and Aβ42 level in the 20,40μmol/L EGCG cells groups were significantly improved compared with the other groups(P<0.05),moreover which showed the concentration dependence(P<0.05).After 20μmol/L EGCG action,the expression levels of LXRβ,RXRαand ABCA1 protein were increased,the expression levels of caveolin-1 and BACE1 protein were significantly decreased,and the differences were statistically significant(P<0.05);after treating the cells by combining with GSK2033,the expression levels of LXRβ,RXRαand ABCA1 protein were significantly decreased and caveolin-1 and BACE1 protein expression levels were significantly increased(P<0.05).Conclusion The generation of Aβ42 in N2a/APP695swe cells could be inhibited by EGCG,thus which inhibits the cellular proliferation,and its mechanism may be related to EGCG activating the LXRβ-RXRα-ABCA1 pathway,and then inhibiting the expression of caveolin-1 and BACE1.

关 键 词：表没食子儿茶素-3-没食子酸酯 Β淀粉样蛋白 LXRβ-RXRα-ABCA1通路 窖蛋白-1 β-分泌酶1 

分 类 号：R741.02[医药卫生—神经病学与精神病学]