原花青素抑制Aβ_(25-35)诱导的人神经母细胞瘤细胞系SH-SY5Y分泌Aβ_(1-42)  

Proanthocyanidins inhibit the secretion of Aβ_(1-42)induced by Aβ_(25-35)in human neuroblastoma cell line SH-SY5Y

作　　者：李琪 张小强[1,2] 陶一凡[1,2] 朱孟雯 崔丹丹 孙腾腾 LI Qi;ZHANG Xiao-qiang;TAO Yi-fan;ZHU Meng-wen;CUI Dan-dan;SUN Teng-teng(School of Public Health,Southeast University,Nanjing 210009,China;Key Laboratory of Environmental Medicine Engineering of Ministry of Education,Southeast University,Nanjing 210009,China)

机构地区：[1]东南大学公共卫生学院,江苏南京210009 [2]东南大学环境医学工程教育部重点实验室,江苏南京210009

出　　处：《基础医学与临床》2021年第5期704-708,共5页Basic and Clinical Medicine

基　　金：中央高校基本科研业务费专项资金资助;江苏省普通高校研究生科研创新计划资助项目(SJZZ160034)

摘　　要：目的研究原花青素(PC)对β-淀粉样肽(Aβ_(25-35))诱导的人神经母细胞瘤细胞系(SH-SY5Y)淀粉样肽产生的影响及可能的作用机制。方法以Aβ_(25-35)体外处理SH-SY5Y细胞诱导细胞损伤模型,应用PC和(或)Wnt/β-catenin信号通路的内源性抑制剂分泌型蛋白Dickkopf-1(Dkk1)干预。设立对照组、Aβ_(25-35)组、不同浓度PC+Aβ_(25-35)组、Dkk1组和Dkk1+PC+Aβ_(25-35)组。MTT法检测细胞活力;Western blot检测β-catenin、GSK-3β和p-GSK-3β蛋白表达水平;ELISA检测Aβ_(1-42)分泌水平。结果与对照组相比,Aβ_(25-35)可使细胞活力降低(P<0.05),可降低细胞中β-catenin蛋白和p-GSK-3β蛋白表达水平(P<0.05),增加细胞中Aβ_(1-42)分泌(P<0.05)。PC干预可改善Aβ_(25-35)导致的细胞活力降低(P<0.05),增加细胞中β-catenin蛋白和p-GSK-3β蛋白表达水平(P<0.05),减少Aβ_(1-42)分泌(P<0.05)。应用Dkk1后,PC提高细胞中β-catenin蛋白和p-GSK-3β蛋白表达水平及降低Aβ_(1-42)分泌水平的能力下降(P<0.05)。结论PC可抑制Aβ_(25-35)诱导的SH-SY5Y细胞Aβ_(1-42)生成,该作用可能与Wnt/β-catenin信号通路有关。Objective To investigate the effect of proanthocyanidins(PC)induced by amyloid-beta peptide(Aβ_(25-35))in human neuroblastoma cell line SH-SY5Y and its possible mechanism.Methods SH-SY5Y cells were exposed to Aβ_(25-35)to establish a cell injury model in vitro.PC and(or)secretory protein Dickkopf-1(Dkk1),the endogenic inhibitor of Wnt/β-catenin signaling pathway were used for intervention.The cells were divided into control group,Aβ_(25-35)group,PC(different concentrations)+Aβ_(25-35)groups,Dkk1 group,Dkk1+PC+Aβ_(25-35)group.The cell viability was evaluated by MTT assay.The expressions ofβ-catenin,GSK-3β,p-GSK-3βwere measured by Western blot.The secreted Aβ_(1-42)was detected by ELISA.Results Compared with the control group,the cell viability,the expression ofβ-catenin and p-GSK-3βwere reduced in Aβ_(25-35)treated group(P<0.05),while the secreted Aβ_(1-42)was increased(P<0.05).PC improved the cell viability,increased the expression ofβ-catenin andp-GSK-3β,and reduced the secreted Aβ_(1-42)in SH-SY5Y cells induced by Aβ_(25-35)(P<0.05).After using Dkk1,the ability of PC was decreased on the enhancement ofβ-catenin expression,the improvement of p-GSK-3βexpression,and the reduction of the secreted Aβ_(1-42)(P<0.05).Conclusions PC may decrease Aβ_(1-42)secretion in SH-SY5Y cells induced by Aβ_(25-35)through Wnt/β-catenin signaling pathway.

关 键 词：原花青素 Aβ_(1-42) WNT/Β-CATENIN 

分 类 号：R749.16[医药卫生—神经病学与精神病学]