铁死亡在铅暴露致小鼠小脑损伤中的作用  

Role of ferroptosis in cerebellar injury of mice following lead exposure

作　　者：王伟轩 赵宇威 师凡 李爽 刘子莹 王唯承 朱毅 张艳淑 Wang Weixuan;Zhao Yuwei;Shi Fan;Li Shuang;Liu Ziying;Wang Weicheng;Zhu Yi;Zhang Yanshu(School of Public Health,North China University of Science and Technology,Tangshan 063210,China;Laboratory Animal Center,North China University of Science and Technology,Tangshan 063210,China;Department of Clinical Medicine,North China University of Science and Technology,Tangshan 063210,China)

机构地区：[1]华北理工大学公共卫生学院,唐山063210 [2]华北理工大学实验动物中心,唐山063210 [3]华北理工大学临床医学系,唐山063210

出　　处：《卫生研究》2022年第3期443-448,469,共7页Journal of Hygiene Research

基　　金：河北省自然基金(No.H2020209250);河北省教育厅科技项目(No.QN2021121,ZD2020113);河北省研究生创新资助项目(CXZZBS2022110)。

摘　　要：目的 探究铁死亡在铅暴露致小鼠小脑损伤中的作用。方法 SPF级雄性C57小鼠40只按体重随机分为对照组和低、中、高浓度铅染毒组,每组10只。铅染毒组小鼠分别饮用0.25、0.50和1.00 g/L乙酸铅溶液共12周,对照组自由饮水。应用电感耦合等离子质谱仪检测小脑中铅含量;应用平衡木和旷场实验检验小鼠的运动平衡能力,用HE染色法观察小鼠小脑病理变化。应用试剂盒检测小鼠小脑组织中铁、丙二醛(malondialdehyde, MDA)和谷胱甘肽(glutathione, GSH)含量;Western blotting法检测小鼠小脑组织中转铁蛋白受体1(transferrin receptor-1, TFR-1)、铁转运蛋白(ferroportin, FPN-1)、溶质载体家族7成员A11 (solute carrier family 7 member A11, SLC7A11)、谷胱甘肽过氧化物酶4 (glutathione peroxidase 4, GPX4)、核因子-E2相关因子(NF-E2-related factor 2,Nrf2)和血红素加氧酶1(heme oxygenase-1, HO-1)蛋白表达情况。结果 低、中、高浓度铅染毒组小鼠小脑铅含量分别为(1.05±0.11)、(1.21±0.10)和(1.48±0.10)μg/g,均显著高于对照组(0.48±0.05)μg/g(P<0.05);平衡木通过时间各染毒组分别为对照组小鼠的1.34、1.64和2.02倍。旷场实验结果显示,各铅染毒组小鼠的中央停留时间和站立次数显著低于对照组。不同剂量铅染毒组小鼠小脑均可见浦肯野细胞排列不规则,胞体变小,深染,其中以高铅组最为明显。低、中和高浓度铅染毒组小鼠小脑中铁含量分别为对照组的1.77、2.29和3.77倍,各铅染毒组小鼠小脑中MDA含量均显著升高,而GHS含量明显下降。与对照组比较,铅染毒组小鼠小脑中铁转入蛋白TFR-1蛋白表达均显著升高,而铁转出蛋白FPN-1蛋白只有中和高浓度铅染毒组的表达下降明显,为对照组的60%和50%。此外,中和高浓度铅染毒组小脑中氧化应激调控蛋白SLC7A11和GPX4蛋白表达均显著下降;各铅染毒组小鼠小脑中Nrf2和HO-1蛋白的表达均降低,但高铅组下降最为�OBJECTIVE To investigate the role of ferroptosis in cerebellar injury of mice following lead exposure.METHODS A total of forty SPF C57 mice were randomly divided into control group,low-dose lead exposure group,middle-dose lead exposure group and high-dose lead exposure group,with 10 mice in each group.Mice in three lead exposure groups were given 0.25,0.50,1.00 g/L lead acetate through drinking water for twelve weeks respectively.Lead concentration was detected by inductively coupled plasma mass spectrometer.The motor function was detected by beam walking test and open field test.Pathological changes of cerebellum in mice were observed by H&E staining.Western blotting was used to detect the protein expression of transferrin receptor-1(TFR-1),ferroportin(FPN-1),solute carrier family 7 member 11(SLC7A11),glutathione peroxidase 4(GPX4),NF-E2-related factor 2(Nrf2)and heme oxygenase-1(HO-1).RESULTS The lead concentration in cerebellum of mice in low lead group,medium lead group and high lead group were(1.05±0.11),(1.21±0.10)and(1.48±0.1)jxg/g,respectively,which were significantly higher than that in the control group.The time to traverse the beam in low lead group,medium lead group and high lead group was 1.34,1.64 and 2.02 folds of that in control group,respectively.Open field test showed that the central residence time and standing times of mice in low lead group,medium lead group and high lead group were significantly lower than that in control.Purkinje cells in the cerebellum of mice exposed to different doses of lead showed irregular arrangement,small cell bodies and deep staining,especially in the high lead group.The relative levels of iron in low lead group,medium lead group and high lead group was 1.77,2.29 and 3.77 folds of that in control group,respectively.The content of MDA in cerebellum of mice in three lead exposure groups increased significantly,while the GHS decreased significantly.Compared with the control group,the expression of TFR-1 protein increased significantly in the lead exposure group,whi

关 键 词：铅暴露 小脑 浦肯野细胞 运动功能 铁死亡 

分 类 号：R113[医药卫生—公共卫生与预防医学] R114