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.

中文翻译：

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Nrf2 对高脂饮食小鼠铅暴露后认知功能障碍的作用。

铅 (Pb) 暴露会对中枢神经系统 (CNS) 造成严重的损害。也有人提出高脂饮食对学习记忆、认知功能有一定的不良影响，但对铅与高脂饮食共同暴露对中枢神经系统损害的研究尚缺乏。本研究旨在探讨Pb对高脂饮食小鼠认知功能的影响，并探讨Nrf2信号通路是否作用于大脑皮层。C57BL/6J小鼠随机分为对照组、高脂饮食、Pb（饮水含250 mg/L醋酸铅）、高脂饮食含Pb（饮水含250 mg/L醋酸铅）共暴露组12 周。实验数据表明，Pb和高脂饮食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、NADP（H）：脱氢酶醌1和超氧化物歧化酶2的蛋白表达显着降低。本研究表明，Nrf2 信号通路的下调可能与铅和高脂饮食共同暴露引起的认知功能障碍有关。