十溴联苯醚母源性暴露影响仔鼠学习记忆能力的机制

Effects of maternal exposure to brominated diphenyl ethers-209 on learning and memory skill in filial generation rats

目的 探讨母鼠妊娠期及哺乳期十溴联苯醚暴露对仔鼠学习记忆能力影响的可能作用机制. 方法 将妊娠第1天的10周龄雌性SD大鼠40只随机分为5组,每组8只.A组：空白对照组（正常饲养）;B组：精炼花生油灌胃5 ml/（kg·d）;C组、D组及E组分别予1、5、10 mg/ （kg·d）十溴联苯醚灌胃（溶于等量精炼花生油）.B组、C组、D组及E组母鼠自妊娠第1天至仔鼠断乳（分娩后28d）每日按上述剂量灌胃.灌胃结束后每组随机选取20只仔鼠（雌雄各半）,用Morris水迷宫对其学习记忆能力进行检测;Morris水迷宫测试结束后,每组上述仔鼠取海马组织,采用实时荧光定量聚合酶链反应法和蛋白质印迹法检测海马组织丝切蛋白-1（Cofilin-1）及波形蛋白（Vimentin） mRNA及蛋白表达水平.采用析因方差分析、单因素方差分析、独立样本f检验、秩和检验、Kruskal-Wallis检验进行统计学分析. 结果 与A组比较,D组及E组仔鼠平均逃避潜伏期时间延长（P＜0.05）;与A组（1.000±0.000）比较,C组、D组及E组仔鼠海马组织Cofilin-1 mRNA的相对定量值[（0.888±0.045）、（0.787±0.041）及（0.610±0.021）]均下降（f值分别为-2.904、-4.555及-3.131,P值均＜0.05）;与A组（1.000±0.000）比较,C组、D组及E组仔鼠海马组织Vimentin mRNA的相对定量值[（0.634±0.031）、（0.428±0.022）及（0.291±0.034）]均下降（t值分别为-20.168、-45.852及-36.457,P值均＜0.01）;与A组（1.60±0.37）比较,D组及E组仔鼠海马组织Cofilin-1蛋白表达水平[（0.88±0.14）及（0.37±0.13）]均下降（f值分别为3.152及5.432,P值均＜0.05）;与A组（1.52±0.20）比较,D组及E组仔鼠海马组织Vimentin蛋白表达水平[（0.51±0.22）及（0.22±0.18）]均下降（f值分别为5.884及8.368,P值均＜0.01）. 结论 妊娠期及哺乳期母鼠十溴联苯醚暴露导致仔鼠学习记忆能力下降,其机制可能与海马组织Cofilin-1及Vimentin mRNA及蛋白表达水平下降有关.

Objective To investigate the effects of maternal exposure to brominated diphenyl ethers-209 （BDE 209） on learning and memory ability in filial generation rats.Methods Forty 10-week-old pregnant SD rats on the first gestation day （G0） were randomly divided into five groups （8 rats per group）.Group A：control group （normal feeding）; Group B：Peanut oil 5 ml/（kg · d） by gavage; Groups C,D and E：1,5 and 10 mg/（kg · d） BDE 209,respectively,by gavage,which was dissolved in an equal amount of peanut oil.The rats in groups B.C,D and E were gavaged from G0 to weaning （28 d after giving birth）.Then,20 offspring （10 males and 10 females） in each group were randomly selected to determine their learning and memory ability using the Morris water maze.After completion of the Morris water maze test,the hippocampus from the offspring in each group was obtained to determine the levels of mRNA and protein expression of Cofilin-1 and Vimentin genes.Results Compared with the control group,the mean escape latency of the offspring in group D and E was prolonged （P＜0.05）.Compared with the control group （1.000±0.000）,the mRNA expression levels of Cofilin-1 in group C （0.888±0.045）,D （0.787±0.041） and E （0.610±0.021） were decreased （t=--2.904,-4.555 and-3.131,all P＜0.05）,and the mRNA expression levels of Vimentin in group C （0.634±0.031）,D （0.428±0.022） and E （0.291 ±0.034） were also decreased （t=-20.168,-45.852 and-36.457,all P＜0.01）.Compared with the control group （1.60±0.37）,the protein expression levels of Cofilin-1 in group D （0.88±0.14） and E （0.37±0.13） were decreased （t=3.152,5.432,all P＜0.05） ; and compared with the control group （1.52± 0.20）,the protein expression levels of Vimentin in group D （0.51 ± 0.22） and E （0.22±0.18） were also decreased （t=5.884,8.368,all P＜0.05）.Conclusion Exposure to BDE-209 during pregnancy and lactation results in a decline in learning and memory ability in rat offspring.This might be related to a decline in the mRNA and protein expression of Cofilin-1 gene and Vimentin gene in offspring hippocampus.