纳米氧化铝急性染毒对小鼠学习记忆能力的影响

Nano-alumina acute exposure on the ability of learning and memory of mice

目的探讨不同粒径的纳米氧化铝(nano-Al2O3)急性染毒对小鼠学习记忆能力的影响。方法选取90只健康成年ICR小鼠,每组18只,分为溶剂对照组(生理盐水)、13 nm Al2O3组、50 nm Al2O3组和10μm Al2O3组。用灌胃法进行急性染毒,染毒剂量均为5 g/kg,染毒后观察期分别为3、7和14 d。第14天观察期结束后用Morris水迷宫对小鼠进行学习记忆能力检测。处死小鼠,取脑,测脑体比,分离皮质,检测炎症因子和氧化应激水平。结果与溶剂对照组相比,各染毒组小鼠体重及脑体比差异均无统计学意义;水迷宫结果显示,13 nm Al2O3组与其余各组相比,学习记忆能力显著下降,差异有统计学意义(P<0.05);炎症因子结果显示:与溶剂对照组相比,炎症因子[首先在第3天肿瘤坏死因子-α(TNF-α)、第7天白介素1-β(IL-1β)]显著升高,各组差异均有统计学意义(P<0.05),且有随粒径减小含量显著增加的趋势(P<0.05);但在第14天时,各组恢复到溶剂对照组水平。氧化应激结果显示,与溶剂对照组相比,各组的丙二醛(MDA)含量在第3天没有显著差异,从第7天开始显著增加,到第14天达到最高水平,差异有统计学意义(P<0.05);且有随粒径减小含量显著增加的趋势(P<0.05).与溶剂对照组相比,各组超氧化物歧化酶(SOD)活力从第3天开始随时间延长逐渐降低,到第14天观察期结束降到最低水平,差异有统计学意义(P<0.05);且有随粒径减小其活力显著降低的趋势(P<0.05)。结论纳米氧化铝可以降低小鼠的学习记忆能力,炎症因子是这一过程中的早期事件,而氧化应激水平的升高可能是学习记忆能力下降的主要原因之一。

[Objective]To investigate the effect of acute exposure of the nano-Al2O3 particles of different size on learning and memory ability of mice.[Methods] A total of 90 adult and health ICR mice of were randomly divided into solvent control group（physiological saline）,13 nm Al2O3 group（5 g/kg）,50 nm Al2O3 group and 10 μm Al2O3 group,with 18 mice in each group.Each was treated by acute lavage,exposure dose was 5 g / kg.They were observed for 3 days,7days,14 days after exposure.Among the group of 14 days,the Morris water maze test was performed to test the learning and memory ability of mice.Mice were killed at the end of the observation,their brains were taken to determine the brain-to-body mass ratio,and separated the cortex for the detection of oxidative stress and inflammatory cytokine response of each one.[Results]Compared with the solvent control group,there was no significant difference on the body weight and brain-to-body mass ratio of mice in the exposed groups.The results of water maze test showed that the difference of learning and memory ability was significant between 13 nm Al2O3 group and other groups（P0.05）.The result of inflammatory cytokines showed comparing with the solvent control group,the TNF α（on the 3 d） and IL-1β（on the 7 d） were significantly increased in 13 nm Al2O3 group,with significant difference between groups（P0.05） and the content increased with the decreasing of the nano Al2O3 particles（P 0.05）.However,the inflammatory factor was restored to the level of the solvent control group in each group on 14 d.Oxidative stress result showed there was significant differences（P0.05）of MDA content in the exposed groups,showing no significant difference on the 3 d,obvious increase from the 7d and reached the maximum on the 14 d,with significant difference（P0.05）and the content increased with the decreasing of the nano Al2O3 particles（P0.05）.Compared with the control group,the activity of SOD decreased with the time elapse from the 3 d,and reached the minimum in exposed group on the 14 d,with significant difference,and the activity decreased with the decreasing of the nano Al2O3 particles（P0.05）.[Conclusion]The nano Al2O3can reduce the ability of learning and memory in mice,inflammatory factors is an early event in this process,elevated level of oxidative stress may be one of the main reasons for the decline of learning and memory ability.