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  

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

作　　者：张群峰 何浣滢 廖云豪 王国卿 ZHANG Qun-feng;HE Huan-ying;LIAO Yun-hao;WANG Guo-qing(College of Life and Health Sciences,Northeastern University,Shenyang,110819,China)

机构地区：[1]东北大学生命科学与健康学院,沈阳110819

出　　处：《神经药理学报》2019年第6期1-5,共5页Acta Neuropharmacologica

基　　金：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,COX2)、环磷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。方法:将母鼠随机分成对照组(control)、溶剂组(cpf0)和给药组,给药组根据给药剂量不同又分为三个亚组,即cpf0.3组、cpf0.6组和cpf1.2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)。结论: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。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,cpf0.3 group,cpf0.6 group and cpf1.2 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 fluorescence 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 increased,while the expression of CREB and BDNF decreased(P<0.01,P<0.05). 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.

关 键 词：毒死蜱 海马 COX2 CREB BDNF 

分 类 号：R741.02[医药卫生—神经病学与精神病学]