铁超载调控氧化性低密度脂蛋白诱导泡沫细胞促动脉粥样硬化活化的作用  

Iron overload regulates atherosclerotic activity of foam cells induced by oxLDL

作　　者：王晓燕 邹小义 祝翔 王婷[3] 强叶涛 周思源 张鹏 张平 WANG Xiaoyan;ZOU Xiaoyi;ZHU Xiang;WANG Ting;QIANG Yetao;ZHOU Siyuan;ZHANG Peng;ZHANG Ping(Department of Clinical Laboratory,The Affiliated Changzhou NO.2 People′s Hospital of Nanjing Medical University,Changzhou 213000,China;不详)

机构地区：[1]南京医科大学附属常州第二人民医院检验科,江苏常州213000 [2]德安医院康复科,江苏常州213000 [3]江苏省人民医院检验科,南京210029 [4]扬中市人民医院检验科,江苏镇江212200

出　　处：《实用医学杂志》2024年第3期295-301,共7页The Journal of Practical Medicine

基　　金：国家自然科学基金项目(编号:82000678);南京医科大学科技发展基金项目(编号:NMUB2020071,NMUB2018062,NMUB2019315)。

摘　　要：目的探讨铁超载对泡沫细胞促动脉粥样硬化(AS)活化的影响。方法RAW264.7和MOVAS细胞株扩增培养,分为正常对照(media)组、oxLDL组、oxLDL+柠檬酸铁铵(oxLDL+FC)组、oxLDL+柠檬酸铁铵+去铁胺(oxLDL+FC+DFO)组,分别以氧化性低密度脂蛋白(oxLDL)、柠檬酸铁胺(FC)、去铁胺(DFO)刺激。普鲁士蓝和油红O染色检测铁沉积和泡沫细胞生成。CCK-8测定细胞存活率,DHE探针观察活性氧自由基(ROS)生成,ELISA测定还原型谷胱甘肽(GSH)、谷胱甘肽过氧化物酶4(GPX4),丙二醛(MDA)含量。RT-qPCR检测ATP结合盒转运体A1(ABCA1)和ATP结合盒转运体G1(ABCG1)、诱导型一氧化氮合酶(iNOS)、精氨酸酶1(Arg-1)、平滑肌肌动蛋白(α-SMA),平滑肌22a(smooth muscle 22 alpha,SM22a)、骨桥蛋白(OPN),白细胞介素-1β(IL-1β)、肿瘤坏死因子-α(TNF-α)mRNA表达。结果与oxLDL组相比,oxLDL+FC组细胞胆固醇逆向转运分子ABCA1和ABCG1表达降低,细胞泡沫化加重,死亡率上升,且ROS和MDA的表达增加,GPX4表达降低,巨噬细胞M1型标志物及平滑肌细胞合成型标志物升高,炎症因子IL-1β、TNF-α的表达明显增加,差异有统计学意义(P<0.05)。结论铁超载能促进泡沫细胞生成,使其向促动脉粥样硬化表型转化,加重脂质过氧化及炎症反应。Objective To explore the roles of iron overload in pro⁃atherogenic activation of foam cells.Methods RAW264.7 and MOVAS cells were stimulated by oxLDL,ferrimine citrate and deferoxamine respectively.Prussian Blue and Oil Red O staining were used to detect iron deposition and foam cell.CCK⁃8 test,DHE probe,ELISA,RT⁃qPCR were performed to detect the cell death rate,reactive oxygen species(ROS)generation,lipid peroxidation molecules[glutathione peroxidase(GSH),glutathione peroxidase 4(GPX4),malondialdehyde(MDA)content]and the mRNA level of ATP binding cassette transporter A1(ABCA1),ATP binding cassette transporter G1(ABCG1),inductible nitris oxide synthase(iNOS),arginase⁃1(Arg⁃1),α⁃smooth muscle actin(α⁃SMA),smooth muscle 22 alpha(SM22a),osteopontin(OPN),Interleukin⁃1β(IL⁃1β),tumor necrosis factor⁃α(TNF⁃α).Results Iron overload could reduced reverse cholesterol transporters(ABCA1 and ABCG1),promote foam cells generation,increased cell death rate,induced the expression of lipid peroxidation molecules(GSH,GPX4,MDA),and promoted pro⁃inflammatory M1 marker of macrophage and synthetic marker expression of vascular smooth muscle cell(VSMC)and inflammatory cytokines(IL⁃1β,TNF⁃α).Conclusion Iron overload promotes the generation of foam cells derived from macrophages and smooth muscle cells and transform them into pro⁃atherosclerotic phenotype,aggravates cell lipid peroxidation and inflammatory reaction,which contributes to the progress of atherosclerosis.

关 键 词：铁超载 泡沫细胞 炎症 脂质过氧化 氧化性低密度脂蛋白 

分 类 号：R543.5[医药卫生—心血管疾病]