神经药理学报

• 研究论文 •    下一篇

母源毒死蜱暴露对子代小鼠海马 COX2、 CREB 和 BDNF mRNA 及蛋白表达的影响

张群峰,何浣滢,廖云豪,王国卿   

  1. 东北大学,生命科学与健康学院,沈阳,110819,中国
  • 出版日期:2019-12-26 发布日期:2020-03-03
  • 通讯作者: 王国卿,E-mail:wangguoqing@mail.neu.edu.cn
  • 作者简介:张群峰,男,本科生;研究方向:动物发育毒理;E-mail:2318015076@qq.com
  • 基金资助:
    国家自然科学基金项目(No.31272615),东北大学大学生创新训练计划项目(No.181100)

The Effects of Maternal Chlorpyrifos Exposure on the Expression of COX2,CREB and BDNF in Hippocampus of Offspring Mice

ZHANG Qun-feng,HE Huan-ying,LIAO Yun-hao,WANG Guo-qing   

  1. College of Life and Health Sciences,Northeastern University,Shenyang,110819,China
  • Online:2019-12-26 Published:2020-03-03
  • Contact: 王国卿,E-mail:wangguoqing@mail.neu.edu.cn
  • About author:张群峰,男,本科生;研究方向:动物发育毒理;E-mail:2318015076@qq.com
  • Supported by:
    国家自然科学基金项目(No.31272615),东北大学大学生创新训练计划项目(No.181100)

摘要:

目的: 研究母源毒死蜱(chlorpyrifos,CPF)暴露对子代小鼠环氧化酶 -2(cyclooxygenase-2,CO 腺苷效应元件结合蛋白(cyclic adenosine monophosphate response element-binding protein,CREB)和脑源性神经营 养因子(brain-derived neurotrophic factor,BDNF)mRNA 及蛋白表达的影响。 将母鼠随机分成对照组(control)、 方法: 溶剂组(cpf )和给药组,给药组根据给药剂量不同又分为三个亚组,即 cpf 0.3 组、cpf 0.6 组和 cpf 1.2 组。母鼠染毒交配 产仔后,应用高效液相色谱(high performance liquid chromatography,HPLC)方法检测母代和子代小鼠血浆中 CPF 浓度,荧光定量 PCR 方法和 Western blot 方法检测子代小鼠海马 COX2、CREB 和 BDNF mRNA 及蛋白的表达量。 结果: 与对照组和溶剂组相比,母鼠进行 CPF 染毒后,母代和子代小鼠血浆中均能检测到 CPF,并且给药组间存在 剂量关系(P<0.01);子代小鼠海马 COX2 mRNA 与蛋白的表达量升高,CREB 与 BDNF mRNA 及蛋白的表达量降 低(P<0.01, P<0.05) 。 CPF可由母代小鼠进入子代体内,通过影响COX2-CREB-BDNF通路产生神经毒性作用。

关键词: 毒死蜱, 海马, COX2, CREB, BDNF

Abstract:

Objective: To study the effects of maternal chlorpyrifos(CPF)exposure on the expression of COX2,CREB and BDNF in offspring of mice. Methods: Female mice were randomly divided into control group,solvent group(cpf0 )and administration group. The administration group was divided into three subgroups according to the dosage,namely,cpf 0.3 group,cpf 0.6 group and cpf 1.2 group. After maternity,5 litters were selected from each group. The concentration of CPF in plasma of mother and offspring mice was determined by HPLC,and the expression of COX2,CREB and BDNF in hippocampus of offspring mice was measured by ?uorescence quantitative PCR and Western blot. Results: Compared with the control group and solvent group,CPF was detected in the plasma of mother and offspring mice after CPF exposure,and there was a dose relationship between the two groups(P<0.01). The expression of COX2 and protein in hippocampus of offspring mice P<0.05) increased,while the expression of CREB and BDNF decreased(P<0.01, . Conclusions: CPF can act on the hippocampus of offspring mice through placental barrier and lactation pathway, and activate COX2-CREB-BDNF pathway to produce toxic effects.

Key words: chlorpyrifos, hippocampus, cyclooxygenase-2(COX2), cAMP-response element binding protein(CREB), brain derived neurotrophic factor(BDNF)

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