Wang Meiyue, Zuo Yong, Li Xincheng, Li Yan, Thirupathi Anand, Yu Peng, Gao Guofen, Zhou Changhao, Chang Yanzhong, Shi Zhenhua
Laboratory of Molecular Iron Metabolism, College of Life Science, Hebei Normal University, Shijiazhuang 050024, Hebei Province, China.
Faculty of Sports Science, Ningbo University, Ningbo 315211, China.
Brain Res. 2021 Apr 15;1757:147328. doi: 10.1016/j.brainres.2021.147328. Epub 2021 Feb 2.
Sevoflurane (Sev), a commonly used volatile anesthetic, could induce nerve damage and cognitive deficiency. Oxidative stress induced by iron overload promotes nerve damage and cell apoptosis in the brain. This study revealed a new toxic mechanism of Sev to the brain occurred through the dysfunction of iron metabolism. Twelve-month-old C57BL/6 mice were randomly assigned to the following three groups: control group; 2% Sev (6 h) group; and Sev plus iron deficiency group. Iron levels and iron metabolism-related proteins and apoptosis-related factors in hippocampus and cortex tissues were detected by using synchrotron radiation micro-X-ray fluorescence (μ-XRF) and western blotting. Our results showed that a decline in cognitive function was observed in mice treated with Sev. Sev significantly induced iron accumulation through upregulating ferritin and downregulating transferrin receptor 1 which involved in ferroportin1 (Fpn1)/hepcidin pathway and increasing reactive oxygen species (ROS) and malondialdehyde (MDA) content of hippocampus and cortex. Sev aggravated BACE1 expression and Aβ accumulation. Changes in the ratio of Bcl2/Bax and Tau/p-Tau intensified the cell apoptosis in hippocampus and cortex tissues. Interestingly, the cognitive deficiency and neurotoxicity induced by Sev could be ameliorated significantly by feeding a low-iron diet to mice prior to anesthesia. The data uncovered a new lesion mechanism of Sev from the role of iron metabolism. This study also suggested that the reduction in iron levels could protect the brain against neurological damage induced by Sev.
七氟醚（Sev）是一种常用的挥发性麻醉剂，可导致神经损伤和认知缺陷。铁过载诱导的氧化应激会促进脑内神经损伤和细胞凋亡。本研究揭示了七氟醚通过铁代谢功能障碍对脑产生的一种新的毒性机制。将12月龄的C57BL/6小鼠随机分为以下三组：对照组；2%七氟醚（6小时）组；七氟醚加缺铁组。采用同步辐射微X射线荧光（μ-XRF）和蛋白质免疫印迹法检测海马和皮质组织中的铁水平、铁代谢相关蛋白及凋亡相关因子。结果显示，七氟醚处理的小鼠出现认知功能下降。七氟醚通过上调铁蛋白、下调参与铁转运蛋白1（Fpn1）/铁调素途径的转铁蛋白受体1，显著诱导铁蓄积，并增加海马和皮质中的活性氧（ROS）和丙二醛（MDA）含量。七氟醚加重了β-分泌酶1（BACE1）的表达和β-淀粉样蛋白（Aβ）的蓄积。Bcl2/Bax和Tau/p-Tau比值的变化加剧了海马和皮质组织中的细胞凋亡。有趣的是，在麻醉前给小鼠喂食低铁饮食可显著改善七氟醚诱导的认知缺陷和神经毒性。这些数据从铁代谢的作用方面揭示了七氟醚一种新的损伤机制。本研究还表明，降低铁水平可保护大脑免受七氟醚诱导的神经损伤。
