铁死亡在微塑料和锰联合暴露致小鼠纹状体损伤的实验研究  

Experimental study of ferroptosis in striatum damage in mice induced by co-exposure of microplastics and manganese

作　　者：吴桐 倪凯月 何新蕾 焦柯影 王玉君 王伟轩 赵良君 郝瀚 张艳淑 WU Tong;NI Kai-yue;HE Xin-lei;JIAO Ke-ying;WANG Yu-jun;WANG Wei-xuan;ZHAO Liang-jun;HAO Han;ZHANG Yan-shu(School of Medical Sciences,North China University of Science and Technology,Tangshan,Hebei 063210,China;不详)

机构地区：[1]华北理工大学临床医学院,河北唐山063210 [2]华北理工大学公共卫生学院 [3]唐山市传染病医院 [4]华北理工大学河北省煤矿卫生与安全重点实验室 [5]华北理工大学实验动物中心 [6]华北理工大学基础医学院

出　　处：《现代预防医学》2024年第20期3774-3780,3815,共8页Modern Preventive Medicine

基　　金：中央引导地方科技发展资金项目(236Z7728G)。

摘　　要：目的通过建立微塑料和锰联合暴露小鼠模型,探讨铁死亡在微塑料和锰联合暴露致纹状体损伤中的作用。方法SPF级雄性C57小鼠40只随机分为对照组、锰暴露组、微塑料暴露组和联合暴露组;应用转棒实验、旷场实验、糖水偏好实验检测小鼠神经行为变化;应用试剂盒检测小鼠纹状体中二价铁离子、丙二醛(malondialdehyde,MDA)和谷胱甘肽(glutathione,GSH)的含量;应用Western blotting法检测小鼠纹状体中铁死亡相关蛋白溶质载体家族7成员11(solute carrier family 7 member,SLC7A11)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、铁泵蛋白(Ferroportin1,FPN1)的蛋白表达;应用实时荧光定量PCR法检测miR-124的表达。多组数据比较采用单因素方差分析,进一步两两比较采用LSD检验。结果行为学实验结果显示,与对照组比较,锰暴露组、微塑料暴露组小鼠的转棒停留时间(均P<0.001)、旷场实验中央区域停留时间(均P<0.001)、总路程(均P<0.001)、糖水偏好率(P_(锰)=0.010;P微塑料<0.001)均显著下降;与单独锰暴露组或微塑料暴露组比较,联合暴露组转棒停留时间、旷场实验中央区域停留时间、总路程均显著降低(均P<0.001);此外,联合暴露组小鼠的糖水偏好率低于锰暴露组(P=0.001)。同时,与对照组比较,锰暴露组、微塑料暴露组小鼠纹状体中Fe^(2+)含量升高(P_(锰)=0.002;P微塑料=0.001),GSH含量降低(P_(锰)=0.015;P微塑料<0.001),且微塑料暴露组小鼠纹状体中MDA含量升高(P<0.001);此外,联合暴露组小鼠纹状体中Fe^(2+)、MDA含量高于锰暴露组(P_(Fe2)^(+)=0.004;P_(MDA)<0.001)和微塑料暴露组(P_(Fe2)^(+)=0.008;P_(MDA)=0.007),GSH含量低于锰暴露组(P<0.001);锰暴露组(P=0.010)、微塑料暴露组(P=0.001)小鼠纹状体中SLC7A11蛋白表达均低于对照组;微塑料暴露组GPX4蛋白表达低于对照组(P=0.007),联合暴露组GPX4蛋白表达低于锰暴露组(P=0.006);此外,锰暴露组(P=0.005)�Objective To investigate the role of ferroptosis in striatum damage induced by combined exposure of microplastics and manganese by establishing a mouse model following microplastics and manganese alone or combined exposure.Methods Forty SPF male C57 mice were randomly divided into control group,manganese exposure group,microplastics exposure group and combined exposure group.Neurobehavioral tests including rotarod test,open field test and sucrose preference test were performed.The contents of divalent iron,malondialdehyde and glutathione in striatum of mice were detected by using the kit.Western blotting was used to detect the protein expressions of SLC7A11,GPX4 and FPN1 in striatum of mice.Real-time PCR was performed to detect the expression of miR-124.Single factor analysis of variance was used for comparison of multiple groups of data,and LSD test was used for further pairwise comparison.Results Behavioral tests showed that the residence time of the rotating rod(all P<0.001),the residence time in the central zone of open field test(all P<0.001),total distance of open field test(all P<0.001)and the sucrose preference rate(P_(manganese)=0.010;P_(microplastics)<0.001)in manganese exposure group and microplastics exposure group decreased significantly compared with that of the control group.Compared with the manganese exposure group and microplastics exposure group,the residence time of the rotating rod,the residence time in the central zone of the open field test and the total distance of the open field test of combined exposure group decreased significantly(all P<0.001).In addition,the sucrose preference rate of the combined exposure group was lower than that of the manganese exposure group(P=0.001).At the same time,compared with the control group,the contents of Fe^(2+)in striatum of mice in manganese exposure group and microplastics exposure group increased(P_(manganese)=0.002;P_(microplastics)=0.001),the contents of GSH decreased(P_(manganese)=0.015;P_(microplastics)<0.001).The content of MDA in the striatum

关 键 词：微塑料 锰暴露 神经损伤 

分 类 号：R-33[医药卫生]