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

doi:10.3969/j.issn.2095-1396.2019.06.001

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

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

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/Abstract

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）

中图分类号:

R741.02

张群峰,何浣滢,廖云豪,王国卿. 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[J]. 神经药理学报, DOI: 10.3969/j.issn.2095-1396.2019.06.001.

ZHANG Qun-feng，HE Huan-ying，LIAO Yun-hao，WANG Guo-qing. The Effects of Maternal Chlorpyrifos Exposure on the Expression of COX2，CREB and BDNF in Hippocampus of Offspring Mice[J]. Acta Neuropharmacologica, DOI: 10.3969/j.issn.2095-1396.2019.06.001.

参考文献

[1] 赵敏娴. 经皮暴露毒死蜱的生理毒代动力学和毒效应学（PBTK/TD）模型研究[D]. 南京：东南大学, 2015.
[2] E M Tanvir E M, Rizwana Afroz, M A Z Chowdhury, et al. A model of chlorpyrifos distribution and its biochemical effects on the liver and kidneys of rats [J]. Human & Experimental Toxicology, 2016, 35(9): 991-1004.
[3] Chen De-chun, Yao H, Xing H, et al. Effects of atrazine and chlorpyrifos on oxidative stress-induced autophagy in the immune organs of common carp (Cyprinus carpio L.) [J]. Fish & Shellfish Immunology, 2015, 44(1): 12-20.
[4] Jonas G Silva, Ana C Boareto, Anne K Schreiber, et al. Chlorpyrifos induces anxiety-like behavior in offspring rats exposed during pregnancy[J]. Neuroscience Letters, 2017, 641:94-100.
[5] 杨朝菊, 王树松. 毒死蜱联合氯氰菊酯染毒对小鼠学习记忆能力的影响[J]. 现代预防医学, 2017(14):133-137.
[6] 张阔, 杨静玉, 吴春福. 抑郁症的病理生理学基础及动物模型研究进展[J]. 神经药理学报, 2017,7(4):8-16.
[7] Richard A Fenske, Fayssal M Farahat, Kit Galvin, et al. Contributions of inhalation and dermal exposure to chlorpyrifos dose in Egyptian cotton field workers [J]. International J Occupational & Environmental Health, 2012, 18(3): 198-209.
[8] Sachana M, Flaskos J, Sidiropoulou E, et al. Inhibition of extension outgrowth in differentiating rat C6 glioma cells by chlorpyrifos and chlorpyrifos oxon: Effects on microtubule proteins [J]. Toxicology in Vitro, 2008, 22(5): 1387-1391.
[9] Ulrike Böer, Christine Noll, Irmgard Cierny, et al. A common mechanism of action of the selective serotonin reuptake inhibitors citalopram and fluoxetine: Reversal of chronic psychosocial stress-induced increase in CRE/CREB-directed gene transcription in transgenic reporter gene mice [J]. European J Pharmacology, 2010, 633(1-3): 33-38.
[10] 李学龙, 梁惠, 姜雨杉，等. 蜂胶对酒精暴露小鼠认知功能损伤的改善效果研究[J]. 神经药理学报, 2019(4):26.
[11] Qiao Hui, An Shu-cheng, Xu Chang. Research progress of BDNF and depression[J]. Progress in Physiological Sciences, 2011, 42(3): 195-200.
[12] Heath D Schmidt, Ronald S Duman. Peripheral BDNF produces antidepressant-like effects in cellular and behavioral models [J]. Neuropsychopharmacology Official Publication of the American College of Neuropsychopharmacology, 2010, 35(12): 2378-2391.
[13] 李爱师. 抑郁症信号转导通路研究[J]. 中国医药科学, 2012, 2(24): 31-33.
[14] Chen Qi, Luo Ying, Kuang Sheng-nan, et al. Cyclooxygenase-2 signalling pathway in the cortex is involved in the pathophysiological mechanisms in the rat model of depression[J]. Scientific Reports, 2017, 7(1):488.

[1]	武春阳，马佳呈，张楠，等. 氨基酸分析仪法批量测定小鼠皮质和海马中氨基酸类神经递质和牛磺酸的含量[J]. 神经药理学报, 2019, 9(5): 10-16.
[2]	WANG Wei-sheng，JU Yun-yue，WANG Yu-jun，LIU Jing-gen. The Small GTPase Rac1 Contributes to Extinction of Aversive Memories of Drug Withdrawal by Facilitating GABAA Receptor Endocytosis in the vmPFC[J]. 神经药理学报, 2018, 8(5): 65-66.
[3]	张耀东，张碧琼，吴文宁，等. 慢性地塞米松对海马神经元损伤及NLRP-1炎症小体激活的影响[J]. 神经药理学报, 2017, 7(3): 47-47.
[4]	方仪德，何祖燕，陈丹，陈圣敏，楚敏，隋璐，董杨. 老年性聋模型小鼠认知功能的下降及其机制探讨[J]. 神经药理学报, 2017, 7(3): 55-55.
[5]	张楠，熊文雯，邢媛，张炜. 大鼠海马神经元及星形胶质细胞的体外培养[J]. 神经药理学报, 2017, 7(1): 24-28.
[6]	何娜，殷明，王泽剑. 成年海马神经再生与阿尔茨海默病关系的研究进展[J]. 神经药理学报, 2013, 3(6): 25-32.
[7]	李炜, 李婷婷, 齐赛卿, 张癸荣. 快速眼球运动睡眠剥夺对记忆和突触可塑性的影响及其分子机制的研究进展[J]. 神经药理学报, 2013, 3(4): 47-57.
[8]	金灿, 张丹参. 应用均匀设计-高通量筛选技术评价丹参有效单体成分抗氧化及海马神经细胞保护作用的最佳配伍[J]. 神经药理学报, 2013, 3(3): 8-14.
[9]	曾靖, 薛进华, 黎晓, 黄志华. 3'-大豆苷元磺酸钠对去血清所致海马神经元损伤的保护作用[J]. 神经药理学报, 2013, 3(3): 15-18.
[10]	YAO Guang-Yin, JI Dan-Yang, ZHOU Wei-Dong, YAO Hai-Yan, KU Bao-Shan, YANG Dong-H. Secoisolariciresinol Reduces Behavioral Despair and Regulates Hippocampal BDNF Expression in Ovariectomized Mice[J]. 神经药理学报, 2013, 3(2): 13-25.
[11]	金灿, 张丹参, 陈乃宏. 成年海马神经元再生与抑郁症的机制研究进展[J]. 神经药理学报, 2013, 3(2): 58-64.
[12]	李晓峰，赵大鹏，陈树沙，景玮，李新毅. 远志总皂苷对AD模型大鼠海马nAChRα4及PSD-95表达的影响[J]. 神经药理学报, 2011, 1(3): 16-22.
[13]	宋金艳，张力，赵晓倩，宋志斌. 大黄酚脂质体对脑缺血再灌注损伤小鼠海马神经元凋亡的影响[J]. 神经药理学报, 2011, 1(2): 7-13.
[14]	徐剑文，杨渐，俞昌喜. 实验性阿尔茨海默病小鼠海马中磷酸酶及张力蛋白同源基因水平的变化[J]. 神经药理学报, 2011, 1(2): 19-23.
[15]	陈琳，杜力军，赵玉男. 糖皮质激素与海马结构可塑性[J]. 神经药理学报, 2011, 1(2): 58-64.

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

PDF (PC)

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 15

编辑推荐

Metrics