宫内砷暴露小鼠对子代小鼠记忆能力及焦虑抑郁样行为的影响  

Effects of intrauterine arsenic exposure on memory ability,anxiety and depression-like behavior in mice

作　　者：张颖 吕媛 乔文瑾 刘瑞刚 邰大鹏 ZHANG Ying;LüYuan;QIAO Wen-jin;LIU Rui-gang;TAI Da-peng(Department of Public Health,Bao Tou Medical College,Inner Mongolia University of Science and Technology,Bao Tou,Inner Mongolia 014040,China)

机构地区：[1]内蒙古科技大学包头医学院公共卫生学院,内蒙古包头014000

出　　处：《环境与健康杂志》2025年第3期195-202,F0003,共9页Journal of Environment and Health

基　　金：内蒙古高等学校科学研究项目(NJZY18187);包头医学院自然科学基金项目青苗计划(BYJJ-ZRQM 202325);内蒙古自然科学基金(2022MS08040)。

摘　　要：目的研究宫内砷(As)暴露(intrauterine arsenic exposure,IAsE)对子代小鼠记忆力减退(MD)及焦虑抑郁样行为(ADB)的影响,并探讨其与继代遗传效应与雄性遗传的关系。方法将40只妊娠SPF级ICR小鼠随机分为4组,分别为对照(去离子水)组和0.05 mg/L、0.5 mg/L、5 mg/L亚砷酸钠染毒组,每组10只。于GD0至分娩,孕鼠采用自然饮水方式进行染毒。IAsE小鼠饲养60 d后进行后续实验。同时将IAsE雄鼠与正常雌鼠合笼获得IAsE雄鼠子代,饲养60 d后进行后续实验。分别进行水迷宫实验、旷场实验、强迫游泳实验及悬尾实验,检测小鼠MD、ADB发生情况;取脑组织做组织切片染色观察海马体组织结构改变;采用qPCR法检测海马体组织中凋亡相关基因bcl-2、bax、caspase-3的表达情况。结果与对照组相比,0.05 mg/L、0.5 mg/L、5 mg/L亚砷酸钠染毒组IAsE小鼠及其雄鼠子代到达平台区域的潜伏期明显延长,在平台区域逗留的时间明显减短,到达平台区域的次数减少,差异均有统计学意义(P<0.05);且随着亚砷酸钠染毒浓度的升高,IAsE小鼠及其雄鼠子代到达平台区域的潜伏期呈延长趋势,在平台区域逗留的时间和到达平台区域的次数均呈下降趋势。强迫游泳实验及悬尾实验结果均显示,与对照组相比,0.05 mg/L、0.5 mg/L、5 mg/L亚砷酸钠染毒组IAsE小鼠及其雄鼠子代在后4 min内的静止不动时间均显著增加,差异有统计学意义(P<0.05);且随着亚砷酸钠染毒浓度的升高,IAsE小鼠及其雄鼠子代的静止不动时间呈上升趋势。HE切片结果显示,IAsE小鼠及其雄鼠子代雄性海马体组织中细胞数减少、排列结构紊乱、细胞形态皱缩。与对照组相比,0.5 mg/L、5 mg/L亚砷酸钠染毒组IAsE雄性小鼠海马体组织bcl-2 mRNA的表达水平降低,而IAsE雌性小鼠海马体组织bax和caspase-3 mRNA的表达水平均升高,差异均有统计学意义(P<0.05);0.5 mg/L、5 mg/L亚砷酸钠染毒组IAsE雄性小鼠Objective To understand the effects of intrauterine arsenic exposure(IAsE)on memory loss(MD)and depression-like behavior(ADB)in offspring mice,and to explore its relationship with genetic effects of subculture and male inheritance.Methods Forty pregnant SPF ICR mice were randomly divided into four groups:control group(deionized water)and 0.05 mg/L,0.5 mg/L,5 mg/L sodium arsenite exposure groups,with 10 mice in each group.From GD0 to delivery,pregnant rats were exposed to natural drinking water.Subsequent experiments were performed after IAsE mice were fed for 60 days.At the same time,IAsE male mice were caged with normal female mice to obtain IAsE male offspring.After 60 days of feeding,follow-up experiments were carried out.Water maze test,open field test,forced swimming test and tail suspension test were performed to detect the occurrence of MD and ADB in mice.The brain tissue was taken for pathological examination of hippocampal tissue.The expression of apoptosis-related genes bcl-2,bax and caspase-3 in hippocampus was detected by qPCR.Results Compared with the control group,the incubation period of IAsE mice and their male offspring in 0.05 mg/L,0.5 mg/L and 5 mg/L sodium arsenite exposure groups was significantly prolonged,the time of staying in the platform area was significantly shortened,and the number of times reaching the platform area was reduced,with significant differences(P<0.05).With the increase of sodium arsenite concentration,the latency of IAsE mice and their male offspring to reach the platform area showed a prolonged trend,and the time spent in the platform area and the number of times reached the platform area showed a downward trend.Compared with the control group,the immobility time of IAsE mice and their male offspring in 0.05 mg/L,0.5 mg/L and 5 mg/L sodium arsenite exposure groups increased significantly within the last 4 min,with significant difference(P<0.05).With the increase of sodium arsenite concentration,the immobility time of IAsE mice and their male offspring showed an upward t

关 键 词：宫内砷暴露 记忆力减退 焦虑抑郁样行为 

分 类 号：R994.6[医药卫生—毒理学]