孕期精神压力与铅复合暴露对子代大鼠恐惧性记忆的影响  

Impact of maternal gestation combined exposure to lead and mental stress on offspring’s fear-conditioning memory

作　　者：黄丽桦 徐健[1,2] 张怡静 刘军霞 HUANG Li-hua;XU Jian;ZHANG Yi-jing;LIU Jun-xia(MOE & Shanghai Key Lab of Children's Environmental Health, Xinhua Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200092, China;TheInternational Peace Maternity & Child Health Hospital, Shanghai Jiao Tong University School of Medicine, Shanghai 200030, China)

机构地区：[1]上海交通大学医学院附属新华医院教育部及上海市环境与儿童健康重点实验室,上海200092 [2]上海交通大学医学院附属国际和平妇幼保健院儿童保健科,上海200030

出　　处：《上海交通大学学报（医学版）》2019年第9期940-946,940,共7页Journal of Shanghai Jiao tong University:Medical Science

基　　金：国家自然科学基金面上项目（81673189,30901205）;上海市教育委员会高峰高原学科建设计划（20172016）;上海市卫生和计划生育委员会项目(201640363)~~

摘　　要：目的·在孕期铅暴露的基础上,探讨孕期精神压力是否对铅在子代的血液、骨骼中的蓄积有增强作用;探讨孕期压力、铅和铅–压力复合暴露对子代恐惧性记忆的影响。方法·将孕鼠随机分为对照组、压力暴露组、铅暴露组、铅–压力暴露组,分娩后每组保留仔鼠12只,雌雄各半。子代大鼠3周龄时通过条件恐惧实验评估仔鼠对条件性恐惧记忆的消退过程,4周龄时处死子代大鼠,提取静脉血、胫骨,以原子吸收光谱法检测血铅水平,以电感耦合等离子质谱仪检测骨铅水平。运用方差分析比较各组间血铅、骨铅及恐惧记忆水平,运用Logistic回归模型分析血铅、骨铅与恐惧记忆的关系。结果·铅暴露组(P血铅=0.013,P骨铅=0.000)、铅–压力复合暴露组(P血铅=0.000,P骨铅=0.000)血铅和骨铅水平均高于对照组。压力暴露组血铅水平略高于对照组(P血铅=0.056),但差异无统计学意义;压力暴露组骨铅水平显著高于对照组(P骨铅=0.004)。铅–压力复合暴露的血铅、骨铅水平较铅暴露组有所上升,但差异无统计学意义(P血铅=0.682,P骨铅=0.124)。与低血铅组、低骨铅组相比,更高的血铅/骨铅组的幼鼠在条件恐惧测试中第二时间段(P=0.008/P=0.016)和第三时间段(P=0.019/P=0.005)高恐惧反应的可能性显著增大。铅–压力复合暴露组在条件恐惧测试中第一时间段([83.73±25.47)%]、第二时间段([92.97±15.75)%]的僵直时间比率分别显著高于对照组第一时间段([65.35±28.80)%,P1=0.048]和第二时间段([68.78±27.22)%,P2=0.021]。结论·孕期铅–压力复合暴露较铅暴露有进一步升高子代血铅、骨铅的趋势。母孕期铅暴露抑制子代大鼠恐惧性记忆消退过程,且这一效应可能被复合的压力暴露所加强。Objective · To explore whether prenatal stress can enhance the accumulation of blood/bone lead in the offspring on the basis of prenatal lead exposure, and to compare the effects of prenatal single exposures to stress/lead and prenatal combined exposure to lead and stress on fear-conditioning memory in the offspring. Methods · Pregnant rats were randomly divided into control group, stress exposure group, lead exposure group and combined lead-stress exposure group. After delivery, each group contained twelve pups (male:female=1:1). The extinction process of fear-conditioning memory was evaluated by the fear-conditioning test in the offspring at 3 weeks old. The offspring were then sacrificed at 4 weeks old. Blood and tibia samples were collected, blood lead was measured by using the atomic absorption spectrometer, and tibia lead was measured by using the inductively coupled plasma–mass spectrometry. The levels of blood lead, bone lead and fear memory were compared by analysis of variance, and the relationship between blood lead, bone lead and fear memory were analyzed by Logistic regression model. Results · The levels of blood and bone lead in the lead exposure group (P blood lead=0.013, P bone lead=0.000) and combined exposure group (P blood lead=0.000, P bone lead=0.000) were significantly higher than those in the control group;the level of blood lead in the stress group was higher but not significantly different from that in the control group (P blood lead=0.056) and the level of bone lead in the stress group was significantly higher than that in the control group (P bone lead=0.004);the levels of blood and bone lead in combined exposure group were higher than those in the lead exposure group, but the differences didn’t reach statistical significance (P blood lead=0.682, P bone lead=0.124). Compared with young rats in the lowest blood lead/bone lead groups, young rats in the groups of higher blood/bone lead levels had higher odds ratios of high fear reaction during the second (P=0.008/ P=0.016) and the t

关 键 词：孕期压力 铅暴露 铅-压力复合暴露 条件恐惧 

分 类 号：R729[医药卫生—儿科]