阿特拉津对SD大鼠黑质TH和Nurr1基因表达的影响

doi:10.3969/j.issn.1004-616x.2016.01.005

癌变·畸变·突变 ›› 2016, Vol. 28 ›› Issue (1): 23-26,31.doi: 10.3969/j.issn.1004-616x.2016.01.005

阿特拉津对SD大鼠黑质TH和Nurr1基因表达的影响

何茜, 李俨书, 李百祥

哈尔滨医科大学公共卫生学院卫生毒理学教研室, 黑龙江哈尔滨 150081

收稿日期:2015-10-12 修回日期:2015-12-15 出版日期:2016-01-31 发布日期:2016-01-31
通讯作者: 李百祥,E-mail:libaix@ems.hrbmu.edu.cn E-mail:libaix@ems.hrbmu.edu.cn
作者简介:何茜,E-mail:315069617@qq.com。
基金资助:
国家自然科学基金资助项目(81273109)

Effect of atrazine on expression of TH and Nurr1 genes in the substantia nigra of Sprague-Dawley rats

HE Xi, LI Yanshu, LI Baixiang

Department of Toxicology, College of Public Health, Harbin Medical University, Harbin 150081, Heilongjiang, China

Received:2015-10-12 Revised:2015-12-15 Online:2016-01-31 Published:2016-01-31

摘要/Abstract

摘要： 目的: 探讨阿特拉津(ATR)对大鼠多巴胺神经元代谢途径中相关因子表达的影响及多巴胺神经元的损伤机制。方法: 清洁级成年雄性SD大鼠68只,随机分为4组,即对照组和ATR 50、100、200 mg/kg剂量染毒组,每组17只。染毒组大鼠经口灌胃ATR 28 d,取大鼠脑组织,分别采用实时荧光定量PCR(qPCR)和免疫组化检测黑质内酪氨酸羟化酶(TH)与核受体相关因子1(Nurr1) mRNA和蛋白表达量的变化,采用 SPSS 17.0进行统计学分析。结果: qPCR结果显示,用50、100和200 mg/kg浓度的ATR染毒的大鼠,其黑质内TH和Nurr1 mRNA表达量与对照组比较明显减少(P<0.05),且存在剂量反应关系。免疫组化结果显示ATR染毒组大鼠黑质中Nurr1、TH蛋白与对照组比较显著降低(P<0.05)。结论: ATR可能通过影响多巴胺神经元代谢途径中的相关酶及其调控酶形成的基因致大鼠多巴胺神经元损伤。

关键词: 阿特拉津, 多巴胺神经元, 酪氨酸羟化酶, 核受体相关因子1

Abstract: OBJECTIVE: We evaluated the effects of atrazine(ATR) exposure in Sprague Dawley rat on the dopaminergic system. METHODS： Healthy adult male SD rats were randomly divided into four groups,control and ATR-dose (50,100,200 mg/kg) groups. Rats were treated orally with ATR for 28 d. The mRNA and protein expression of tyrosine hydroxylase (TH) and nuclear receptor-related factor 1 (Nurr1) were examined in samples of the substantia nigra by fluorescence PCR and immunohistochemistry. We use SPSS 17.0 to analyse the experimental results. RESULTS： qPCR results showed that with 50,100 and 200 mg/kg concentration of ATR exposure,rat substantia nigra TH and Nurr1 mRNA expression was significantly reduced compared with control group (P<0.05),and there was a dose-response relationship. Immunohistochemistry showed that substantia nigra Nurr1 and TH proteins in treated-rats were significantly lower than those among the control group (P<0.05). CONCLUSION： The reduction of Nurr1 and TH suggests that ATR may influence the metabolism of dopamine neurons in dopaminergic neuron injury.

Key words: atrazine, dopaminergic neurons, tyrosine hydroxylase, nuclear receptor-related factor 1

中图分类号:

R114

何茜, 李俨书, 李百祥. 阿特拉津对SD大鼠黑质TH和Nurr1基因表达的影响[J]. 癌变·畸变·突变, 2016, 28(1): 23-26,31.

HE Xi, LI Yanshu, LI Baixiang. Effect of atrazine on expression of TH and Nurr1 genes in the substantia nigra of Sprague-Dawley rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2016, 28(1): 23-26,31.

参考文献

[1] 吉中困,范璞. 帕金森病与帕金森综合征的诊断和治疗[J]. 山东医药,2009,49(31):104-105.
[2] 崔冶,张云龙,王秀艳,等. 佳木斯地区长残效除草剂应用现状及对策思考[J]. 现代化农业,2007,20(9):1-2.
[3] Eldridg JC,Tennant MK,Wetzel LT,et al. Factors affecting mammary tumor incidence in chlorotriazine-treated female rats:hormonal properties,dosage,and animal strain. Environ [J]. Heath Perspect,1994,102:29-36.
[4] 弓爱君,叶常明. 除草剂阿特拉津(Atrazine)的环境行为综述[J]. 环境科学进展,1997,5(2):37-47.
[5] Li Y,Sun Y,Yang J,et al. Age-dependent dopaminergic dysfunction following fetal exposure to atrazine in SD rats[J]. Environ Toxicol Pharmacol,2014,37(3):1275-1282.
[6] Li Y,Sun Y,Yang J,et al. The long-term effects of the herbicide atrazine on the dopaminergic system following exposure during pubertal development[J]. Mutat Res Genet Toxicol Environ Mutagen,2014,763:23-29.
[7] Ma K,Wu HY,Zhang B,et al. Neurotoxicity effects of atrazine-induced SH-SY5Y human dopaminergic neuroblastoma cells via microglial activation[J]. Mol Biosyst,2015,11(11): 2915-2924.
[8] 陈锡群. 酪氨酸羟化酶与帕金森病[J]. 国外医学:神经外科学分册,2001,28(1):59-62.
[9] 张晓录,张逢春,李尧华. 酪氨酸羟化酶与帕金森病的关系研究[J]. 北华大学学报:自然科学版,2006,6(3):224-227.
[10] Zetterstrom RH,SolominL,Jansson L,et al. Dopamine neuron agenesis in Nurrl deficient mice[J]. Science,1997,276 (5310):248-250.
[11] Saucedo-Cardenas O,Quintana-Hau JD,Le WD,et al. Nurrl is essential for the in duction of the dopaminergic phenotype and the survival of ventral mesencephalic late dopaminergic precursor neurons[J]. Proc Natl Acad Sci USA 1998,95(7):4013-4018.
[12] Castillo SO,Baffi JS,Palkovits M,et al. Dopamine biosyn-thesis is selectively abolished in substantia nigra/ventral tegmental area but not in hypothalamic neurons in mice with targeted disruption of the Nurr1 gene[J]. Mol Cell Neurosci 1998,11(1/2):36-46.
[13] Kim JH,Auerbach JM,Rodriguez-Gomez JA,et al. Dopamine neurons derived from embryonic stem cells function in an animal model of Parkinson's disease[J]. Nature,2002 418(6893): 50-56.
[14] Castro DS,Hermanson E,Joseph B,et al. Induction of cell cycle arrest and morphological differentiation by Nurr1 and retinoids in dopamine MN9D cells[J]. J Biol Chem,2001 276(46):43277-43284.
[15] Kim JY,Koh HC,Lee JY,et al. Dopaminergic neuronal differentiation from rat embryonic neural precursors by Nurr1 overexpression[J]. J Neurochem,2003,85(6):1443-l454.
[16] 吴云成,蔡友庆,赵永波,等. 核受体相关因子1表达下调对多巴胺能细胞酪氨酸羟化酶和神经突起生长的影响[J]. 生理学报,2006,58(4):351-358.
[17] 马莉,陈汶,高晓虹,等. 农业环境因素与帕金森病关系的病例对照研究[J]. 中国神经精神疾病杂志,2005 31(1):11-13.
[18] 石夜明,黄玉哲,杜向青,等. 环境因素与帕金森病的关系[J]. 现代中西医结合杂志,2008,17(25):4038-4039.
[19] 刘剑,赵菁,郑晶莹,等. 除草剂阿特拉津体内生物学毒性的研究进展[J]. 吉林大学学报:医学版,2012,38(6): 1236-1240.
[20] Zetterstrom RH,Solomin L,Jansson L,et al.Dopamine neuron agenesis in Nurr1-deficient mice[J].Science,1997 276(5310):248-250.
[21] Kim KS,Kim CH,Hwang DY,et al. Orphan nuclear receptor Nurr1 directly transactivates the promoter activity of the tyrosine hydroxylase gene in a cell-specific manner[J]. J Neurochem 2003,85(3):622-634.

阿特拉津对SD大鼠黑质TH和Nurr1基因表达的影响

Effect of atrazine on expression of TH and Nurr1 genes in the substantia nigra of Sprague-Dawley rats

PDF

可视化

摘要/Abstract

引用本文

使用本文

参考文献

相关文章 3

编辑推荐

Metrics

本文评价

[1]	李鹏, 马焜, 吴浩宇, 吴艳萍, 李百祥. 大豆异黄酮对阿特拉津损伤SH-SY5Y细胞的保护作用及其机制[J]. 癌变·畸变·突变, 2018, 30(1): 25-30.
[2]	马焜, 吴昊宇, 李鹏, 王丽, 李百祥. 阿特拉津对青春期大鼠黑质区多巴胺能神经元的损伤作用[J]. 癌变·畸变·突变, 2017, 29(4): 251-255.
[3]	李家男, 宋肖垚, 吴沿萍, 李百祥. 阿特拉津对大鼠多巴胺神经元凋亡相关因子表达的影响[J]. 癌变·畸变·突变, 2015, 27(2): 121-124.