铅染毒致高血压小鼠小脑铁死亡  

Cerebellar ferroptosis of hypertension mice following lead exposure

作　　者：张子祎 郝瀚 王泽明 赵宇威 王伟轩 庞淑兰 张艳淑 Zhang Ziyi;Hao Han;Wang Zeming;Zhao Yuwei;Wang Weixuan;Pang Shulan;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;School of Life Sciences,North China University of 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]华北理工大学生命科学学院,唐山063210

出　　处：《卫生研究》2024年第4期547-552,共6页Journal of Hygiene Research

基　　金：国家自然科学基金(No.82073598);中央支持地方项目(No.236Z7728G)。

摘　　要：目的 探讨高血压小鼠铅染毒后小脑铁死亡变化。方法 选取25只健康C57雄性小鼠腹腔注射血管紧张素Ⅱ(Ang II)0.05 mg/kg连续7 d的方法构建高血压模型,当收缩压≥140 mm Hg后,取20只高血压小鼠随机分为高血压对照组、高血压铅染毒组。另取20只正常血压的C57小鼠随机分为血压正常对照组与血压正常铅染毒组。血压正常对照组与高血压对照组小鼠自由饮水,血压正常铅染毒组和高血压铅染毒组小鼠饮用含250 mg/L乙酸铅饮水,高血压对照组与高血压铅染毒组小鼠每两天一次腹腔注射Ang II,共12周。采用旷场实验和平衡木实验检测小鼠运动功能障碍情况;应用试剂盒检测不同组别小鼠小脑中二价铁(Fe^(2+))、丙二醛(malondialdehyde,MDA)和谷胱甘肽(glutathione,GSH)含量;采用Western blot法测定小鼠小脑组织中溶质载体家族7成员11(solute carrier family 7 member 11,SLC7A11)、谷胱甘肽过氧化物酶4(glutathione peroxidase 4,GPX4)、核受体共激活因子4(nuclear receptor coactivator 4,NCOA4)、微管相关蛋白1轻链3B(microtubule associated protein light chain 3B,LC3B)、铁蛋白重链1(ferritin heavy chain 1,FTH1)蛋白表达。结果 旷场实验结果显示,高血压铅染毒组小鼠活动距离(1013.04 cm)显著低于高血压对照组(1351.18 cm)和血压正常铅染毒组(1287.35 cm);且高血压铅染毒组通过平衡木时间也延长,为29.40 s(P<0.05)。此外,高血压铅染毒组小鼠小脑中Fe^(2+)含量为3.33μmol/g prot,是高血压对照组的1.54倍、血压正常铅染毒组的1.14倍;MDA含量为4.71 nmol/mg prot,高于高血压对照组和血压正常铅染毒组;GSH含量为5.36μmol/g prot,低于高血压对照组与血压正常铅染毒组(P<0.05)。Western blot结果显示,与高血压对照组及血压正常铅染毒组比较,高血压铅染毒组SLC7A11和GPX4蛋白表达均显著下降(P<0.05)。此外,与血压正常对照组相比,高血压对照组和血压正常铅染毒组小鼠小脑�OBJECTIVE Exploring the changes in cerebellar ferroptosis in hypertensive mice after lead exposure.METHODS Twenty-five healthy C57 male mice were selected to construct a hypertensive model by intraperitoneal injection of angiotensin II(Ang II) at a concentration of 0.05 mg/kg for 7 consecutive days.After a systolic blood pressure of 140 mmHg,20 hypertensive mice were randomly divided into a hypertensive control group and a hypertensive lead exposure group.Twenty C57 mice with normal blood pressure were randomly divided into a blood pressure normal control group and a blood pressure normal lead exposure group.The mice in the normal blood pressure control group and the hypertensive control group drank water freely.Mice in the lead exposure group with normal blood pressure and the lead exposure group with hypertension drank lead acetate water containing 250 mg/L.Ang II was injected intraperitoneally every two days in the hypertensive control group and hypertensive lead exposed group mice.Each group of mice was poisoned for 12 weeks.Using open field experiments and balance beam experiments to detect motor dysfunction in mice.Using a reagent kit to detect the levels of divalent iron(Fe~(2+)),malondialdehyde(MDA),and glutathione(GSH) in the cerebellum of different groups of mice.Western blot was used to determine the protein expression of member 11 of the solute carrier family 7(SLC7A11),glutathione peroxidase 4(GPX4),nuclear receptor coactivator 4(NCOA4),microtubule associated protein 1 light chain 3B(LC3B),and ferritin heavy chain 1(FTH1) in mouse cerebellar tissue.RESULTS The result of the open field experiment showed that the activity distance(1013.04 cm) of mice in the hypertensive lead exposure group was significantly lower than that of the hypertensive control group(1351.18 cm) and the lead exposure group with normal blood pressure(1287.35 cm).And the lead exposure group with hypertension also extended the time through the balance beam,which was 29.40 seconds(P<0.05).In addition,the Fe~(2+)content in the cerebel

关 键 词：铅 高血压 铁死亡 小脑 铁自噬 

分 类 号：R114[医药卫生—卫生毒理学] R135.11[医药卫生—公共卫生与预防医学]