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Nrf2 在高脂饮食小鼠铅暴露后认知功能障碍中的作用。

The Role of Nrf2 on the Cognitive Dysfunction of High-fat Diet Mice Following Lead Exposure.

机构信息

School of Public Health, North China University of Science and Technology, Tangshan, People's Republic of China.

Experiment Animal Center, North China University of Science and Technology, Tangshan, People's Republic of China.

出版信息

Biol Trace Elem Res. 2021 Jun;199(6):2247-2258. doi: 10.1007/s12011-020-02346-x. Epub 2020 Aug 18.

DOI:10.1007/s12011-020-02346-x
PMID:32812172
Abstract

Lead (Pb) exposure can induce the severe deleterious damage on the central nervous system (CNS). High-fat diet also has been suggested that it had some adverse effects on learning and memory, cognitive function, but there is lack of study on Pb and high-fat diet co-exposure on the CNS damage. In this study, the goal was to explore the effect of Pb on the cognitive function of mice with high-fat diet and to investigate whether Nrf2 signaling pathway acts in the cerebral cortex. C57BL/6J mice were randomly divided into control, high-fat diet, Pb (drinking water with 250 mg/L lead acetate), and high-fat diet with Pb (drinking water with 250 mg/L lead acetate) co-exposure groups for 12 weeks. Experiment data showed that learn memory and exploration ability of mice obviously decreased in Pb and high-fat diet, and reactive oxygen species (ROS) increased; then, the protein expressions of Nrf2, heme oxygenase-1, NADP(H):dehydrogenase quinone 1, and superoxide dismutase 2 were lower significantly compared with those in the control group. This study suggested that down-expressed Nrf2 signaling pathway possibly related to the cognitive dysfunction induced by Pb and high-fat diet co-exposure.

摘要

铅(Pb)暴露会对中枢神经系统(CNS)造成严重的有害损伤。高脂肪饮食也被认为对学习和记忆、认知功能有一些不良影响,但缺乏关于 Pb 和高脂肪饮食共同暴露对中枢神经系统损伤的研究。在这项研究中,目的是探讨 Pb 对高脂肪饮食小鼠认知功能的影响,并研究 Nrf2 信号通路是否在大脑皮层中起作用。C57BL/6J 小鼠被随机分为对照组、高脂肪饮食组、Pb(饮用水中含有 250mg/L 醋酸铅)组和 Pb 与高脂肪饮食共同暴露组(饮用水中含有 250mg/L 醋酸铅),共暴露 12 周。实验数据表明,Pb 和高脂肪饮食组小鼠的学习记忆和探索能力明显下降,活性氧(ROS)增加;然后,与对照组相比,Nrf2、血红素加氧酶-1、NADPH:醌 1 和超氧化物歧化酶 2 的蛋白表达明显降低。本研究提示,下调的 Nrf2 信号通路可能与 Pb 和高脂肪饮食共同暴露引起的认知功能障碍有关。

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Developmental lead (Pb)-induced deficits in hippocampal protein translation at the synapses are ameliorated by ascorbate supplementation.补充抗坏血酸可改善发育性铅(Pb)诱导的海马突触蛋白翻译缺陷。
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