急性亚砷酸钠染毒对人肺上皮细胞结构及功能影响研究  

Effect of acute sodium arsenite exposure on barrier structure and function of human pulmonary epithelial cells barrier damage

作　　者：王美文 李乐桐 林加曼 王强 WANG Mei-wen;LI Le-tong;LIN Jia-man;WANG Qiang(School of Public Health,Anhui Medical University,Hefei,Anhui 230032,China;Chinese PLA Center for Disease Control and Prevention,Bejing 100071,China)

机构地区：[1]安徽医科大学公共卫生学院,安徽合肥230032 [2]中国人民解放军疾病预防控制中心,北京100071

出　　处：《毒理学杂志》2024年第6期426-429,436,共5页Journal of Toxicology

基　　金：国家自然科学基金(81973003)。

摘　　要：目的通过细胞模型染毒试验,探讨急性亚砷酸钠染毒对肺上皮细胞结构及功能的影响。方法用A549细胞建立肺上皮细胞模型,分别设10、20、40、60和80μmol/ml NaAsO_(2)染毒组和对照组。采用CCK-8方法测定NaAsO_(2)急性染毒对A549细胞存活率的影响;采用细胞跨上皮电阻法和FITC-右旋糖酐荧光法测定A549细胞层的通透性;Western blot检测检测不同浓度NaAsO_(2)对β-Catenin、E-Cadherin、Occludin紧密连接和黏附连接蛋白的表达情况。结果随着NaAsO_(2)浓度的增加,细胞活力逐渐降低;20、40和60μmol/ml的NaAsO_(2)均可改变A549细胞层的电阻;经FITC-右旋糖酐检测发现40和60μmol/ml的NaAsO_(2)可改变A549细胞层的通透性(F_(40)=9.080,F_(60)=50.265,P<0.05)。随着NaAsO_(2)浓度的增高,E-Cadherin蛋白和Occludin蛋白表达量逐渐降低,β-Catenin蛋白表达量逐渐增加。结论急性亚砷酸钠染毒会改变肺上皮细胞通透性,破坏紧密连接和黏附连接结构。Objective To investigate the effects of acute sodium arsenite exposure on the structure and function of the pulmonary epithelial cell barrier in a cellular model.Methods A549 cells were utilized to establish a pulmonary epithelial barrier model,which was exposed to various concentrations of NaAsO_(2)(10,20,40,60,80μmol/ml)along with a control group.The impact of acute NaAsO_(2) exposure on A549 cell viability was assessed using the CCK-8 assay.The permeability of the A549 cell layer was measured using transepithelial electrical resistance(TEER)and FITC-dextran fluorescence method.Western blot analysis was performed to evaluate the expression levels of tight junction and adherens junction proteins,includingβ-Catenin,E-Cadherin,and Occludin at different NaAsO_(2) concentrations.Results As the concentration of NaAsO_(2) escalated,cellular viability diminished progressively.Concentrations of NaAsO_(2) at 20,40,and 60μmol/ml exhibited the ability to modify the transepithelial electrical resistance(TEER)in A549 cell layer.Assessment using FITC-dextran fluorescence demonstrated that NaAsO_(2) at concentrations of 40 and 60μmol/ml altered the permeability of A549 cell layer(F_(40)=9.080,F_(60)=50.265,P<0.05).Additionally,E-Cadherin and Occludin protein levels decreased,whileβ-Catenin protein levels increased with higher NaAsO_(2) concentrations.Conclusion Acute exposure to sodium arsenite can alter the permeability of pulmonary epithelial cell,disrupting the structure of tight junctions and adherens junctions.

关 键 词：亚砷酸钠 急性染毒 肺上皮细胞 紧密连接 黏附连接 

分 类 号：R114[医药卫生—卫生毒理学] R99[医药卫生—公共卫生与预防医学]