亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

doi:10.3969/j.issn.1004-616x.2021.04.003

癌变·畸变·突变 ›› 2021, Vol. 33 ›› Issue (4): 255-261.doi: 10.3969/j.issn.1004-616x.2021.04.003

亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

王佳敏, 刘建新, 孟庆贺, 郝卫东

北京大学公共卫生学院毒理学系, 食品安全毒理学研究与评价北京市重点实验室, 北京 100191

收稿日期:2021-03-30 修回日期:2021-05-21 出版日期:2021-07-30 发布日期:2021-07-29
通讯作者: 郝卫东,E-mail:whao@bjmu.edu.cn E-mail:whao@bjmu.edu.cn
作者简介:王佳敏,E-mail:wangjiamin@pku.edu.cn。
基金资助:
国家重点研发计划项目（2017YFC1600203）

Sub-chronic exposure to yttrium nitrate on learning and memory functions in female rats

WANG Jiamin, LIU Jianxin, MENG Qinghe, HAO Weidong

Department of Toxicology, School of Public Health, Peking University/Beijing Key Laboratory of Toxicological Research and Risk Assessment for Food Safety, Beijing 100191, China

Received:2021-03-30 Revised:2021-05-21 Online:2021-07-30 Published:2021-07-29

摘要/Abstract

摘要： 目的：观察稀土化合物硝酸钇[Y（NO₃）₃]亚慢性（90 d）暴露对大鼠学习记忆能力的影响，并探究其可能的机制，为全面评估稀土元素钇的健康风险提供科学依据。方法：选用刚离乳（PND21）SD雌性大鼠，根据质量随机分为4组，分别为对照组（ddH₂O），Y（NO₃）₃低剂量组[10 mg/（kg·d）]、中剂量组[40 mg/（kg·d）]和高剂量组[160 mg/（kg·d）]，每组15只。连续灌胃受试物90 d后进行旷场实验、高架十字迷宫实验、转棒实验、Morris水迷宫实验。水迷宫检测后，每组取5只雌鼠心脏原位灌注，进行脑组织病理学检查。每组剩余10只雌鼠摘取脑组织，紫外分光光度计检测雌鼠大脑皮质和海马中谷氨酸（Glu）的含量；Western blot检测海马组织中N-甲基-D-天冬氨酸（NMDA）受体蛋白表达情况。结果：与对照组相比，硝酸钇90 d暴露后，转棒实验中160 mg/（kg·d）剂量组大鼠在棒时间、在棒圈数、掉落速度明显升高（P<0.05）。在Morris水迷宫定位航向实验第4天时，40、160 mg/（kg·d）剂量组大鼠逃避潜伏期明显降低（P<0.05）；Morris水迷宫空间探索实验中，40 mg/（kg·d）剂量组大鼠穿越平台次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组穿越平台次数、进入目标象限次数、目标象限游泳时间明显增加（P<0.05）；160 mg/（kg·d）剂量组大鼠东北、东南、西南象限的逃避潜伏期明显低于西北象限的逃避潜伏期（P<0.05）。160 mg/（kg·d）剂量组大鼠海马中Glu含量和NMDA受体NR1含量均明显低于对照组（P<0.05）。40和160 mg/（kg·d）剂量组大鼠海马中NMDA受体NR2A含量明显低于对照组（P<0.05）。结论：硝酸钇亚慢性（90 d）暴露可以引起雌性大鼠空间学习记忆能力增强；硝酸钇可能通过降低海马组织神经元细胞外Glu含量，抑制NMDA受体激活，增强雌性大鼠的空间学习记忆能力。

关键词: 硝酸钇, 学习记忆, 大鼠, Morris水迷宫实验

Abstract: OBJECTIVE: This study was designed to investigate effects from 90-day exposure of yttrium nitrate on neurobehavioral functions in female rats. METHODS: Female Sprague-Dawley rats (PND 21),weighing 45-55 g each,were randomly divided into 4 groups of 15 rats per group:control (ddH₂O exposure) and exposed groups[10,40,160 mg/(kg·d) of Y(NO₃)₃]. Rats in the exposed group were administered orally with Y(NO₃)₃ for 90 days. Then,all exposed and control rats were evaluated using Open field,Elevated plus maze,Rotarod and Morris water maze tests. After the tests,5 rats per group were perfused in situ. Their brains were removed and fixed for histopathological analyses. The other 10 rats per group were sacrificed. Their brains were removed and the levels of glutamate (Glu) in cerebral cortex and hippocampus were determined using UV-Vis. Protein expression levels of NMDARs in hippocampus were detected by Western blot. RESULTS: After 90 days of Y(NO₃)₃ exposure,the 160 mg/(kg·d) group showed significantly increased average time on the rotarod compared to the control group. In the Morris water maze test,the escape latencies among rats in the 40 and 160 mg/(kg·d) Y(NO₃)₃ groups were significantly reduced compared to that in the control group at the 4th day of navigation test. In the space exploration test of Morris water maze test,the times crossing platform and the times required for swimming in target quadrant were significantly increased in the 40 mg/(kg·d) Y(NO₃)₃ group. The times crossing platform,entering the target quadrant and swimming time in the target quadrant were significantly increased in the 160 mg/(kg·d) Y(NO₃)₃ group. The escape latency of NE,SW and SE quadrants in the 160 mg/(kg·d) Y(NO₃)₃ group was significantly delayed compared to that in NW quadrant. Glu level in hippocampus in the 160 mg/(kg·d) Y(NO₃)₃ group was significantly decreased. Expressions of NMDAR2A in hippocampus were significantly decreased in the 40 and 160 mg/(kg·d) Y(NO₃)₃ groups. Expressions of NMDAR1 in the hippocampus were significantly decreased in the 160 mg/(kg·d) Y(NO₃)₃ group. CONCLUSION: Subchronic (90-day) exposure to Y(NO₃)₃ affected the spatial learning and memory of female rats,possibly by decreasing Glu in the extracellular of hippocampal neurons and by antagonizing the activation of NMDARs.

Key words: yttrium nitrate, learning and memory, rat, Morris water maze test

中图分类号:

R994.6

王佳敏, 刘建新, 孟庆贺, 郝卫东. 亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响[J]. 癌变·畸变·突变, 2021, 33(4): 255-261.

WANG Jiamin, LIU Jianxin, MENG Qinghe, HAO Weidong. Sub-chronic exposure to yttrium nitrate on learning and memory functions in female rats[J]. Carcinogenesis, Teratogenesis & Mutagenesis, 2021, 33(4): 255-261.

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亚慢性硝酸钇暴露对雌性大鼠学习记忆能力的影响

Sub-chronic exposure to yttrium nitrate on learning and memory functions in female rats

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