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经鼻滴注纳米氧化铝颗粒对小鼠认知功能损伤的研究。

A study on cognitive impairment of mice exposed to nano-alumina particles by nasal drip.

机构信息

Department of Occupational Health, School of Public Health, Shanxi Medical University, China.

Department of Occupational Health, School of Public Health, Shanxi Medical University, China; Key Lab of Environmental Hazard and Health of Shanxi Province, Shanxi Medical University, China; Key Lab of Cellular Physiology of Education Ministry, Shanxi Medical University, China.

出版信息

J Trace Elem Med Biol. 2022 Sep;73:127003. doi: 10.1016/j.jtemb.2022.127003. Epub 2022 May 20.

Abstract

BACKGROUND

As an emerging nanomaterial, nano-alumina is widely used in chemical engineering, food and medicine due to its special physical and chemical properties, and its potential health hazards have attracted attention.

OBJECTIVE

Aim of this study is to understanding the effect and possible mechanism of nano-alumina on cognitive function in mice.

METHODS

Male healthy ICR mice were randomly assigned and given nasal drops of saline, nano-alumina (different doses) and micro-alumina for 30 days, respectively. Morris water maze test, step down test and open field test were used to detect learning and memory ability. Blood brain permeability was observed by immunofluorescence staining and lanthanum nitrate tracing, histopathological abnormalities in mice hippocampus was observed by thionine staining, the final determination of oxidative stress level in brain tissue was measured by using oxidative stress index detection kit and the level of LC3-Ⅱ and Caspase-3, 8, 9 proteins were detected by western blot.

RESULTS

In the cerebral cortex of mice exposed to nano-alumina particles, lanthanum nitrate particles adhered to vascular endothelial cells, and the expression of ZO-1 and Occuldin decreased and morphology was disordered; most neurons in hippocampus CA3 region showed balloon-like swelling and degeneration, nucleoli disappeared and apical dendrites broke; mice exposed to nano-alumina, the escape latency in Morris water maze increased compared with the control group(P < 0.05),and the residence time in the original platform quadrant shortened significantly(P < 0.05);the platform latency was significantly shortened and the number of errors increased in the step down test compared with the control group; the residence time in the center of mice the nano-alumina treated was significantly increased in open field test (P < 0.05).

CONCLUSION

The nano-alumina particles could be transported into the central nervous system via blood-brain barrier and olfactory bulb, impair learning and memory function in mice, which is more serious than the micro-alumina particles. The apoptosis of mice neurons caused by nano-alumina particles maybe due to the mixed neurotoxic effect of oxidative stress and the elemental toxicity of aluminum itself.

摘要

背景

纳米氧化铝作为一种新兴的纳米材料,由于其特殊的物理化学性质,被广泛应用于化工、食品和医药领域,其潜在的健康危害也引起了人们的关注。

目的

本研究旨在探讨纳米氧化铝对小鼠认知功能的影响及可能的作用机制。

方法

将雄性健康 ICR 小鼠随机分为生理盐水组、纳米氧化铝(不同剂量)组和微米氧化铝组,分别鼻腔滴注 30 天。采用 Morris 水迷宫实验、跳台实验和旷场实验检测学习记忆能力;免疫荧光染色和硝酸镧示踪观察血脑屏障通透性;硫堇染色观察小鼠海马组织病理改变;氧化应激指标检测试剂盒检测脑组织氧化应激水平;Western blot 检测 LC3-Ⅱ和 Caspase-3、8、9 蛋白的表达。

结果

纳米氧化铝颗粒可透过血脑屏障进入小鼠大脑皮质,硝酸镧颗粒黏附于血管内皮细胞,ZO-1 和 Occludin 表达减少,形态紊乱;海马 CA3 区多数神经元呈气球样肿胀、变性,核仁消失,树突顶端断裂;与对照组比较,纳米氧化铝组小鼠 Morris 水迷宫逃避潜伏期延长(P<0.05),原平台象限停留时间明显缩短(P<0.05);跳台实验中纳米氧化铝组平台潜伏期明显缩短,错误次数增加(P<0.05);旷场实验中纳米氧化铝组小鼠中央格停留时间明显增加(P<0.05)。

结论

纳米氧化铝颗粒可透过血脑屏障和嗅球进入中枢神经系统,导致小鼠学习记忆功能障碍,其损伤作用较微米氧化铝更为明显。纳米氧化铝颗粒引起的小鼠神经元凋亡可能与氧化应激的混合神经毒性作用及铝元素本身的细胞毒性有关。

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