亚砷酸钠对小鼠肝细胞AML12损伤的作用机制  

The mechanism of injury induced by sodium arsenite on mouse hepatocytes AML 12

作　　者：赵哲仪 王正蓉 方兴艳 王甜 罗昭逊[5] 谢婷婷 ZHAO Zheyi;WANG Zhengrong;FANG Xingyan;WANG Tian;LUO Zhaoxun;XIE Tingting(Clinical Laboratory Center,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou,China;School of Clinical Laboratory Science,Guizhou Medicai Unwersity,Guiyang 555004,Guizhou,China;Prenatal Diagnosis Center,the Affiliated Hospital of Guizhou Medical University,Guiyang 550004,Guizhou,China;Department of Clinical Laboratory,Shandong Provincial Third Hospital,Jinan 255031,Shandong,China;Academy of Pediatrics,Guizhou Medical University,Guiyang 555004,Guizhou,China)

机构地区：[1]贵州医科大学附属医院临床检验中心,贵州贵阳550007 [2]贵州医科大学医学检验学院,贵州贵阳550007 [3]贵州医科大学附属医院产前诊断中心,贵州贵阳550007 [4]山东省立第三医院检验科,山东济南250032 [5]贵州医科大学儿科学院,贵州贵阳550007

出　　处：《贵州医科大学学报》2022年第1期1-6,共6页Journal of Guizhou Medical University

基　　金：国家自然科学基金(81560514);贵州省科技创新人才团队项目(2019-5610)

摘　　要：目的探讨亚砷酸钠(NaAsO_(2))对小鼠肝细胞AML12损伤作用的机制。方法取对数生长期的小鼠正常肝细胞AML12,设置6个NaAsO_(2)浓度[0(对照)、10、15、20、25及30μmol/L]组,分别用相应浓度的NaAsO_(2)处理AML12细胞24 h;采用化学比色法和油红O染色法检测各组AML12细胞内丙二醛(MDA)和脂质含量水平,采用实时荧光定量PCR(RT-qPCR)和Western blot法分别检测各组小鼠AML12细胞内法尼醇X受体(FXR)、小异二聚体伴侣(SHP)mRNA和FXR、SHP、Bcl-2相关X蛋白(Bax)蛋白的表达。结果与对照组相比,10-30 μmol/L NaAsO_(2)组小鼠AML细胞内MDA含量升高、但FXR和SHP mRNA及FXR蛋白相对表达量下降(P<0.05),2-33 pmol/L NaAsO_(2)组小鼠AML细胞内脂滴含量增加(P<0.05),20-30 μmol/L NaAsO_(2)组小鼠AML细胞内SHP蛋白相对表达量降低(P<0.05),25-30 μmol/L NaAsO_(2)组小鼠AML细胞内BAX蛋白相对表达量增高(P<0.05)。结论NaAsO_(2)可致小鼠肝细胞AML12损伤,其机制可能与FXR-SHP信号通路的失调有关。Objective To investigate the mechanism of injury induced by sodium arsenite(NaAsO_(2))on mouse hepatocytes AML12.Methods Mouse normal hepatocytes AML12 at logarithmic growth stage were taken and treated with[0(control),10,15,20,25,and 30μmol/L]NaAsO_(2)for 24 h.The contents of intracellular Malondialdehyde(MDA)and lipid droplets in AML12 cells were detected by chemical colorimetry and oil red O staining.The expression of steatosis;farnesoid X receptor(FXR),small heterodimer partner(SHP)mRNA and FXR,SHP,and Bcl-2 related X protein(Bax)were detected by real-time fluorescence quantative PCR and western blot.Results Compared with the control group,MDA content in 10-30μmol/L NaAsO_(2)groups increased(P<0.05),but the relative expression levels of FXR,SHP mRNA and the relative expression levels of FXR protein decreased(P<0.05).Compared with the control group,the lipid droplets content in 15-30μmol/L NaAsO_(2)groups increased(P<0.05),the relative expression of SHP protein in 20-30μmol/L NaAsO_(2)groups increased(P<0.05),the relative expression of BAX protein in 25-30μmol/L NaAsO_(2)groups increased(P<0.05).Conclusion NaAsO_(2)induces mouse hepatocytes AML12 injury which may be related to the dysregulation of FXR-SHP signaling pathway.

关 键 词：细胞凋亡 亚砷酸钠 小鼠肝细胞AML12 氧化应激 脂肪变性 法尼醇X受体 小异二聚体伴侣 

分 类 号：R994.6[医药卫生—毒理学]