昆明医科大学学报2025，Vol.46Issue(11)：18-25,8.DOI:10.12259/j.issn.2095-610X.S20251103
APOE4调控LRP1对Aβ25-35诱导的星形胶质细胞氧化应激和炎症反应的作用
The Role of APOE4 in Regulating LRP1 on Aβ25-35-Induced Oxidative Stress and Inflammatory Response in Astrocytes
摘要
Abstract
Objective To investigate the effect of APOE4 in regulating LRP1 and on β-amyloid protein Aβ25-35-induced oxidative stress and inflammatory response in astrocytes.Methods Human astrocytes were transfected with sh-NC,sh-APOE4,pcDNA-NC,and pcDNA-LRP1,and then induced with 10 μM Aβ25-35 for 24 h to establish an AD cell model.The roles of APOE4 and LRP1 in Aβ25-35-induced oxidative stress and inflammatory response were assessed using Western blot,flow cytometry,the detection kits of MDA,SOD,and GSH,as well as enzyme-linked immunosorbent assay(ELISA)kits for TNF-α,IL-6,and IL-1β.The protein-protein interaction between APOE4 and LRP1 was detected through co-immunoprecipitation and western blot experiments.Results Aβ25-35 induction upregulated APOE4 expression(P<0.01),promoted the levels of ROS(P<0.001),MDA(P<0.001),and inflammatory cytokines TNF-α,IL-6,and IL-1β(P<0.001)in astrocytes,while inhibited the expression of SOD,GSH,and LRP1(P<0.001).Knockdown of APOE4 or overexpression of LRP1 suppressed the Aβ25-35-induced increase in ROS,oxidative stress markers,and inflammatory cytokines in cells(P<0.05).APOE4 negatively regulated LRP1 protein expression through protein-protein interactions.The levels of ROS,MDA,and inflammatory cytokines were higher(P<0.05),and the concentrations of SOD and GSH were lower(P<0.001),in cells with simultaneous knockdown of APOE4 and LRP1 compared to those with APOE4 knockdown alone.Conclusion Knockdown of APOE4 attenuates Aβ25-35-induced oxidative stress and inflammatory response in astrocytes by upregulating LRP1.关键词
阿尔兹海默病/星形胶质细胞/Aβ/氧化应激/炎症反应Key words
Alzheimer's disease/Astrocytes/Aβ/Oxidative stress/Inflammatory response分类
医药卫生引用本文复制引用
李妍平,Fariha Tasnim Efty,陆志星,朱灵英..APOE4调控LRP1对Aβ25-35诱导的星形胶质细胞氧化应激和炎症反应的作用[J].昆明医科大学学报,2025,46(11):18-25,8.基金项目
云南省科技厅重点研发计划项目(202303AC100027) （202303AC100027）
云南省张勇民院士工作站(202305AF150024) （202305AF150024）
