纳米氧化钕致小鼠中枢神经系统毒性效应  

Toxic effects of nano-sized neodymium oxide on central nervous system in mice

作　　者：杨宁 樊鸿星 纪乐[1] 姜珊 刘东杰[1] 杨静[1] 刘扬[1] 吴刚[1] YANG Ning;FAN Hongxing;JI Le;JIANG Shan;LIU Dongjie;YANG Jing;LIU Yang;WU Gang(Baotou Medical College of Preclinical and Forensic Medicine,Inner Mongolia University of Science and Technology,Baotou,Inner Mongolia 014040,China)

机构地区：[1]内蒙古科技大学包头医学院基础医学与法医学院,内蒙古包头014040 [2]乌兰察布医学高等专科学校药学检验系,乌兰察布012000

出　　处：《中国职业医学》2018年第4期471-475,共5页China Occupational Medicine

基　　金：内蒙古自治区自然科学基金项目(2015MS0868);内蒙古自治区研究生科研创新项目[S201710127(Y01)]

摘　　要：目的探讨纳米氧化钕染毒对小鼠中枢神经系统的毒性效应。方法无特定病原级雌性ICR小鼠随机分为对照组、低剂量组和高剂量组,每组12只。采用滴鼻染毒法,低和高剂量组小鼠分别予剂量为80、160 mg/(kg·d)体质量的纳米氧化钕染毒,对照组予等体积0.9%氯化钠溶液,连续染毒30 d。采用水迷宫实验和跳台实验检测小鼠的空间学习和记忆能力,取大脑海马作苏木素-伊红(HE)染色和胶质原纤维酸性蛋白(GFAP)免疫组化染色,采用酶标仪检测脑组织中丙二醛(MDA)水平和总超氧化物歧化酶(T-SOD)活力。结果与对照组比较,低和高剂量组小鼠的逃避潜伏期均延长(P<0.05),跳台潜伏期均缩短(P<0.05)。各组小鼠大脑海马HE染色均未见明显的病理改变。免疫组化染色结果显示,低、高剂量组小鼠海马星形胶质细胞GFAP蛋白表达均较对照组增加,以高剂量组增加更明显。与对照组比较,低和高剂量组小鼠脑组织中MDA水平均升高(P<0.05),SOD水平均下降(P<0.05)。结论纳米氧化钕滴鼻染毒可降低小鼠的学习记忆能力,并可导致海马星形胶质细胞GFAP表达增加,其机制可能与氧化应激有关。Objective To investigate the toxic effects of nano-sized neodymium oxide（ nano-Nd_2O_3） on the central nervous system in mice. Methods Specific pathogen free female ICR mice were randomly divided into control group,lowdose group and high-dose group,with 12 rats in each group. The mice in low-dose group and high-dose group were treated with nano-Nd_2O_3 by nasal drip method at 80 and 160 mg/（ kg·d） body weight for 30 days,while the mice in the control group were given 0. 9% sodium chloride solution. The water maze experiment and jump platform experiment were used to evaluate learning and memory ability. Hippocampus was examined using Hematoxylin-Eosin（ HE） staining and glial fibrillary acidic protein（ GFAP） immunohistochemical staining. The level of malondialdehyde（ MDA） and the activity of total superoxide dismutase（ T-SOD） in brain tissue were detected by microplate reader. Results The escape latency increased and the step down latency decreased in the low-dose group and high-dose group compared with the control group（P 0. 05）. No obvious pathological changes were observed by HE staining in brain hippocampus. Immunohistochemistry staining showed that the expression of GFAP protein in the hippocampal astrocytes of the low-and high-dose groups was higher than that in the control group,especially in the high-dose group,when compared with the control group. The MDA level increased and the T-SOD activity decreased in the low-and high-dose groups compared with the control group（ P 0. 05）. Conclusion nano-Nd2 O3 can reduce the learning and memory ability of mice and increased GFAP expression in hippocampal astrocytes. The mechanism may be related to oxidative stress.

关 键 词：纳米氧化钕 神经系统 神经毒性 学习记忆 海马 氧化应激 丙二醛 超氧化物歧化酶 

分 类 号：R135[医药卫生—劳动卫生]