邻苯二甲酸二丁酯对雄性子代大鼠学习记忆及海马Spinophilin表达的影响  

Effects of DBP on Learning and Memory and Spinophilin Expression in Hippocampus of the F1 Generation Rats

作　　者：李元锋[1] 庄梅株[1] 李涛[1] 胡雄飞[1] 王开亮 王喆 石年[1] 

机构地区：[1]华中科技大学同济医学院公共卫生学院卫生毒理学系,教育部环境与健康重点实验室,湖北武汉430030

出　　处：《癌变．畸变．突变》2008年第5期380-384,共5页Carcinogenesis,Teratogenesis & Mutagenesis

基　　金：国家自然科学基金资助项目(30600485)

摘　　要：背景与目的:观察邻苯二甲酸二丁酯(dibutyl phthalate,DBP)暴露对子代大鼠学习记忆能力的影响和海马spinophilin基因表达的影响。材料与方法:妊娠Wistar大鼠随机分成4组:3个不同DBP剂量(25、75、225 mg/kg)的实验组和溶剂对照组,各组孕鼠于孕第6 d至产后28 d分别给予DBP或溶剂灌胃。观察孕鼠、仔鼠染毒后的基本情况,采用定量PCR检测21 d龄雄性仔鼠海马中spinophilin基因的表达情况,Morris水迷宫实验测试1月龄雄性仔鼠的学习记忆能力。结果:在实验剂量范围内,孕鼠无明显中毒表现;DBP高剂量组(225 mg/kg)雄性仔鼠肛殖距、尾长明显缩短(P<0.01)。在水迷宫实验中,DBP低剂量组(25 mg/kg)仔鼠逃避潜伏期较对照组相对延长(P<0.05),空间搜索试验中目标象限的停留时间也相对缩短(P<0.01)。低剂量组仔鼠海马spinophilin基因的表达较对照组上调35.7%(P<0.05)。结论:DBP孕期和哺乳期暴露会降低子代雄性大鼠的学习记忆能力,促进spinophilin基因的表达,两者之间可能存在一定的联系。BACKGROUND AND AIM: To study the effects of dibutyl phthalate(DBP) exposure on learning and memory of the F1 generation rats,as well as the expression of spinophilin gene in the hippocampus.MATERIALS AND METHODS: Pregnant Wistar rats were randomly divided into 3 experimental groups and control group,each treated with 25、75、225 mg/kg DBP or vehicle only(corn oil) by gavage since gestation day 6 to postnatal day 28.The general effects of DBP on the pregnant rats and the offspring were observed.The expression level of spinophilin gene in hippocampus of the 21 day-old male pups was determined by Real Time RT-PCR,and the learning and memory abilities of the one month-old male pups was evaluated through Morris water maze.RESULTS: No overt sign of toxicity was found in the dams,but the male pups in the high dose group showed shortened AGD and tail length(P<0.01).In the water maze test,latency to find a hidden platform was longer in the low dose group than that of control(P<0.05).The pups in the former group also spent less time in the target quadrant in the probe test(P<0.01).Moreover,the expression of spinophilin gene was up-regulated 35.7% in this group as compared with control(P<0.05).CONCLUSION: In utero and lactational DBP exposure decreased learning and memory of the F1 generation rats,associated with up-regulated spinophilin expression in the hippocampus,suggesting a causal relationship.

关 键 词：邻苯二甲酸二丁酯 学习记忆 水迷宫 spinophilin基因 实时定量RT-PCR 

分 类 号：R741[医药卫生—神经病学与精神病学]