发育期不同阶段铅染毒及对应驱铅治疗对小鼠近远期认知的影响  

Effects of lead exposure and chelation therapy in different developmental stages on mouse short-term and long-term cognitive functions

作　　者：张怡静 周蕾蕾 徐健 颜崇淮[2] 段燕红[3] 曹晓华 ZHANG Yijing;ZHOU Leilei;XU Jian;YAN Chonghuai;DUAN Yanhong;CAO Xiaohua(International Peace Maternity&Child Health Hospital/Shanghai Key Laboratory of Embryo Original Diseases,Shanghai Jiao Tong University School of Medicine,Shanghai 200030,China;Xinhua Hospital/MOE-Shanghai Key Lab of Children’s Environmental Health,Shanghai Jiao Tong University School of Medicine,Shanghai 200092,China;School of Life Sciences/Brain Functional Genomics,Ministry of Education/Shanghai Key Laboratory of Brain Functional Genomics,East China Normal University,Shanghai 200062,China)

机构地区：[1]上海交通大学医学院附属国际和平妇幼保健院/上海市胚胎源性疾病重点实验室,上海200030 [2]上海交通大学医学院附属新华医院/教育部和上海市环境与儿童健康重点实验室,上海200092 [3]华东师范大学生命科学学院/教育部和上海市脑功能基因组学重点实验室,上海200062

出　　处：《环境与职业医学》2021年第11期1251-1257,共7页Journal of Environmental and Occupational Medicine

基　　金：国家自然科学基金项目(81373016,81974486)。

摘　　要：[背景]铅损害儿童的认知发育,但发育期铅暴露是否损害中老年阶段的认知功能,及络合治疗是否减轻发育期铅暴露诱发的认知损害的研究相对较少。[目的]探讨小鼠发育期不同阶段(包括哺乳期、断乳期和性成熟早期)铅暴露及驱铅治疗对小鼠近期和远期认知功能影响的差异。[方法]分别选取哺乳期、断乳期和性成熟早期(2、21和41日龄)C57BL/6雄鼠各30只,随机均分为3组(对照组、铅暴露组和铅暴露后驱铅组)。其中,10只为对照组,给予标准饲料和去离子水饲养;10只为铅暴露组,另10只为铅暴露后驱铅组,后2组均先给予标准饲料和含醋酸铅饮用水(母鼠剂量为0.1%,幼鼠为0.05%),自由饮水摄入,染毒19 d后,铅暴露后驱铅组小鼠再灌胃给予二巯基丁二酸(1 mmol·kg^(–1),每天1次,共6 d)。驱铅结束后(在实验开始25 d后)检测各组小鼠的血铅水平;小鼠75日龄时进行Morris水迷宫实验,记录定位航行试验(75~79日龄)的逃避潜伏期,探索试验(80日龄)的目标象限探索时间和穿台次数来分析对近期认知的影响;小鼠365日龄时,测量海马长时程增强表达,诱导各组小鼠离体脑片的fEPSP幅度来分析铅对远期认知的影响。[结果]各发育阶段3组幼鼠的血铅水平有差异(F_(哺乳期)=43.47,F_(断乳期)=228.6,F_(性成熟早期)=274.2,均P<0.001)。各发育阶段铅暴露组幼鼠的血铅水平均高于各自对照组水平(哺乳期、断乳期和性成熟早期血铅质量浓度(后称浓度)均数分别为386.4、265.0、178.1μg·L^(–1),均P<0.001);驱铅后与各相应阶段的铅暴露组相比,血铅水平明显下降(哺乳期、断乳期和性成熟早期染毒驱铅后的血铅浓度均数分别为28.68、47.29、20.93μg·L^(–1),P均<0.001),且哺乳期铅暴露幼鼠经过驱铅后下降幅度最大(哺乳期、断乳期、性成熟早期分别下降92.58%、82.15%、88.25%,P<0.01)。水迷宫实验中,哺乳期铅暴露组小鼠的逃避潜伏�[Background]Lead(Pb)exposure impairs cognitive functions of children.Whether Pb exposure in different developmental stages induces long-term cognitive impairment,and whether chelation therapy could mitigate the cognitive impairment is rarely reported.[Objective]This experiment is designed to investigate effects of Pb exposure and chelation therapy during different developmental stages(breastfeeding,weaning,and early puberty periods)on mouse short-term and long-term cognitive functions.[Methods]C57BL/6 male mice in breastfeeding period,weaning period,and early puberty period(postnatal day 2,21,and 41;PND 2,PND 21,and PND 41,n=30,respectively)were randomly divided into control,Pb exposure,and Pb+dimercaptosuccinic acid(DMSA)treatment groups(n=10 in each group).The control groups received standard food and deionized water.The Pb exposure mice received standard food and free drinking water containing Pb acetate(0.1%for dams,and 0.05%for pups).After receiving Pb acetate for 19 d,the Pb+DMSA treatment groups were given 1 mmol·kg^(−1)·d^(−1) DMSA for 6 d with gastric infusion.Whole blood Pb levels were measured after DMSA treatment on experimental day 25.The effects on short-term cognitive function were tested in the Morris Water Maze task by the analyses of escape latency on PND 75−79,as well as target quadrant time and times of platform-crossing on PND 80.Hippocampal longterm potentiation of field excitatory postsynaptic potential(fEPSP)of mice on PND 365 was induced to demonstrate the effects on longterm cognitive function.[Results]The blood Pb levels among the Pb,Pb+DMSA,and control groups were statistically different for each developmental stage(F_(breastfeeding period)=43.47,F_(weaning period)=228.6,F_(early period of puberty)=274.2,all P<0.001).Compared to the counterpart control groups,blood Pb levels of the pb exposure groups(386.4,265.0,and 178.1μg·L^(–1) in breastfeeding period,weaning period,and early puberty period,respectively)were significantly higher for all stages.After the chelation therapy

关 键 词：铅 2 3二巯基丁二酸 络合治疗 不同发育阶段 认知功能 长时程增强电位 

分 类 号：R114[医药卫生—卫生毒理学]