DEHP联合铅慢性染毒对小鼠学习记忆能力及APP酶解通路的影响  

Effect of DEHP Combined with Chronic Lead Exposure on Learning and Memory Abilities and APP Enzymatic Pathway of Mice

作　　者：李奇翰 付朝旭 许妍姬[1] LI Qihan;FU Zhaoxu;XU Yanji(Preventive Medicine Department,Yanbian University Medicine School,Yanji,Jilin 133000)

机构地区：[1]延边大学医学院预防医学教研部,吉林延吉133000

出　　处：《智慧健康》2023年第5期54-60,65,共8页Smart Healthcare

基　　金：吉林省中医药科技项目(项目编号:2018-135);吉林省教育厅“十三五”科学技术研究项目基金(项目编号:JJKH20200532KJ)。

摘　　要：目的 探讨邻苯二甲酸二(2-乙基)乙酯(DEHP)与铅(Pb)慢性联合染毒对小鼠学习记忆能力的影响。方法 将80只2个月龄健康雄性昆明种小鼠作为研究对象,将小鼠随机分为正常对照组(CT)组、b组、DEHP染毒组(低、中、高剂量)和DEHP+Pb联合染毒组(低、中、高剂量)共8组,每组5只。分别在小鼠饲料中染毒DEHP,在饮用水中添加乙酸铅染毒12周和24周。在染毒结束后,进行Morris水迷宫实验检测小鼠行为学改变情况,采取ELISA法测定小鼠脑组织中α、β-分泌酶活性及sAPPα与Aβ1-40含量,并对两种物质的联合作用方式进行评价。结果 Morris水迷宫实验结果显示,与CT组比较,12周与24周的DEHP染毒组随着剂量增加小鼠空间学习能力受到的损害更加严重,可导致空间记忆能力障碍,目标象限路程占总路程百分比降低,目标象限游泳时间缩短,潜伏期增加。生化指标表明,与CT组比较,DEHP组和DEHP联合染毒组随剂量增加,α-分泌酶活性、sAPPα含量降低,β-分泌酶活性、Aβ1-40明显增高,24周小鼠表现比12周小鼠更为明显,高剂量组DEHP与Pb联合染毒表现具有一定的拮抗作用。结论 邻苯二甲酸双(2-乙基己基)酯与铅慢性染毒均会对小鼠学习记忆产生损害,对小鼠引起学习记忆能力障碍,DEHP与铅联合染毒具有一定拮抗作用。Objective To investigate effect of chronic combined exposure of bis(2-ethyl)phthalate(DEHP)and lead(Pb)on learning and memory abilities of mice.Methods The paper chose 802-month-old healthy male Kunming mice as research subjects,and divided them into 8 groups randomly:normal control group(CT),Pb group,DEHP exposure group(low,medium,and high dose),and DEHP+Pb combined exposure group(low,medium,and high dose),with 5 mice in each group.Mice were exposed to DEHP in feed and lead acetate in drinking water for 12 and 24 weeks.After exposure,Morris water maze experiment was conducted to detect behavioral changes of mice,and determine contents ofα,β-secretory enzyme activity and sAPPαAnd Aβ1-40 contents with ELISA method,combined action mode between two substances was evaluated.Results Morris water maze experiment showed,spatial learning ability of DEHP exposure group at 12 and 24 weeks was more severely impaired as dose increased than CT group,which could lead to spatial memory impairment,decrease in percentage of target quadrant distance in total distance,decrease in target quadrant swimming time,and increase in latency.Biochemical indicators showed that,α-secretory enzyme activity,sAPPαcontents of DEHP group and DEHP combined exposure group lower with dose increase,β-secretory enzyme activity,Aβ1-40 increased more significantly than CT group,performance of mice at 24 weeks was more significant than those at 12 weeks.DEHP and Pb combined exposure of high-dose group had some certain antagonistic effect.Conclusion Both chronic exposure to bis(2-ethylhexyl)phthalate and lead can damage learning and memory of mice,cause impairment of learning and memory abilities.Combined exposure of DEHP and lead has some certain antagonistic effect.

关 键 词：邻苯二甲酸双(2-乙基己基)酯 铅 联合染毒 神经毒性 

分 类 号：R114[医药卫生—卫生毒理学]