陈艳丽¹,
陈芙蓉¹,
胡元灏²,
蔡子壕²,
晏彪²
1. 三峡大学附属仁和医院药学部, 宜昌 443001;
2. 湖北科技学院基础医学研究中心, 咸宁 437100

作者简介: 陈艳丽(1982-),女,硕士,主管药师,研究方向为临床药理与临床药学,E-mail:46284834@qq.com*通讯作者.

基金项目: 湖北省教育厅科学技术研究项目(B2018172)


中图分类号: R31

Neurobehavioral Effects of Dibutyl-phthalate on KM Mice and the Antagonistic Role of Mangiferin

Chen Yanli¹,
Chen Furong¹,
Hu Yuanhao²,
Cai Zihao²,
Yan Biao²
1. Department of Pharmacy, Affiliated Renhe Hospital of China Three Gorges University, Yichang 443001, China;
2. Research Center of Basic Medical Sciences, Hubei University of Science and Technology, Xianning 437100, China
Fund Project: Supported by the Science and Technology Research Project of Education Department of Hubei Province (B2018172)


CLC number: R31

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摘要:探究邻苯二甲酸二丁酯(DBP)对小鼠神经行为学影响的剂量-反应关系，以及芒果苷(MAG)的拮抗作用。36只性成熟雄性KM小鼠随机分为4组：(1)生理盐水组，(2) 5 mg·kg^-1 DBP组，(3) 25 mg·kg^-1 DBP组，(4)125 mg·kg^-1 DBP组，实验周期28 d。应用国际通用的高架十字迷宫(EPM)和旷场实验(OFT)检测DBP暴露后KM小鼠的神经行为学变化；通过脑组织病理学切片，检测KM小鼠的靶组织脑海马CA1区病理变化；通过测定活性氧(ROS)、谷胱甘肽(GSH)、丙二醛(MDA)、DNA-蛋白质交联系数(DPC)，检测KM小鼠的脑海马组织氧化损伤水平。以MAG作为抗氧化剂，36只KM小鼠随机分为4组：(1)生理盐水组，(2) 50 mg·kg^-1 MAG组；(3) 125 mg·kg^-1 DBP组；(4) MAG+DBP组，进行神经行为测试，同时评估各组KM小鼠脑海马组织氧化损伤。与对照组比较，随着DBP暴露剂量的升高，125 mg·kg^-1 DBP组KM小鼠进入开放臂次数减少，停留时间偏短，运动距离较短，运动轨迹偏离中央区域；脑海马CA1区锥体神经细胞排列紊乱，细胞形态肿胀变形，树突缩短甚至消失；且脑系数下降，ROS、MDA含量及DPC系数逐渐上升，GSH含量逐渐降低，且差异均有统计学意义(P＜0.05, P＜0.01)；加入拮抗剂MAG处理后，与125 mg·kg^-1 DBP组比较，MAG+DBP组小鼠神经行为学出现一定程度的缓解，脑海马CA1区病理程度减轻，脑系数上升，ROS、MDA含量及DPC系数出现一定程度的下降，GSH含量出现一定程度的上升，且差异均有统计学意义(P＜0.05, P＜0.01)。DBP所致小鼠的神经行为学变化可能与脑海马组织的氧化损伤有关；MAG可通过降低小鼠脑组织氧化应激水平，对DBP暴露所致的小鼠神经行为学影响起到一定的保护作用。
关键词: 邻苯二甲酸二丁酯/
芒果苷/
脑组织/
氧化应激/
神经行为学

Abstract:To explore the dose-dependent effects of dibutyl phthalate (DBP) on neurobehavior of laboratory mice as well as the antagonistic effect of mangiferin (MAG), male Kunming mice were treated with saline (control), 5 mg·kg^-1 DBP, 25 mg·kg^-1 DBP, and 125 mg·kg^-1 DBP lasted for 28 days (n=9 for each group). The neurobehavioral changes of KM mice after DBP exposure were evaluated by elevated maze plus maze (EPM) and open field test (OFT), and the pathological changes in the hippocampal CA1 region of Kunming mice were examined by sectioning and H&E staining. Reactive oxygen species (ROS), glutathione (GSH), malondialdehyde (MDA), and DNA-protein crosslinking coefficient (DPC) were also measured in brain tissues of Kunming mice. In addition, Kunming mice were also treated with 50 mg·kg^-1 MAG, 125 mg·kg^-1 DBP and 50 mg·kg^-1 MAG+125 mg·kg^-1 DBP (MAG+DBP) to evaluate the protective effects of MAG. Compared with the control group, the Kunming mice treated with 125 mg·kg^-1 DBP group showed reduced number of entering the open arm, shorter staying time, decreased movement distance, and deviated movement track from the central region. The pyramidal neurons in the CA1 area of hippocampus were disordered, and the cell shape was swollen and deformed, as well as the dendrites were shortened or even disappeared. In addition, the contents of ROS, MDA and DPC coefficients increased gradually, whereas the GSH content decreased accordingly (P＜0.05, P＜0.01). After the treatment with antagonist MAG, the neurobehavioral changes, pathological degree of the CA1 area in the hippocampus of 50 mg·kg^-1 MAG+125 mg·kg^-1 DBP treated mice were alleviated compared with 125 mg·kg^-1 DBP group, accompanied by increased brain organ coefficient. The values of ROS, MDA and DPC coefficient decreased, whereas the GSH content increased accordingly (P＜0.05, P＜0.01). The neurobehavioral changes of mice induced by DBP might be related with oxidative damage of hippocampus, whereas MAG may protect Kunming mice from DBP induced adverse neurobehavioral effects by reducing the oxidative stress in brains of mice.
Key words:dibutyl phthalate/
mangiferin/
brain/
oxidative stress/
neurobehavioral effects.