Chronic intermittent hypoxia (CIH) is a consequence of obstructive sleep apnea (OSA), which increases reactive oxygen species (ROS) generation, resulting in oxidative damage and neurocognitive impairment. This study was designed to determine whether abnormal iron metabolism occurs in the brain under conditions of CIH and whether Huperzine A (HuA) could improve abnormal iron metabolism and neurological damage. The mouse model of CIH was established by reducing the percentage of inspired O2 (FiO2) from 21% to 9% 20 times/h for 8 h/day, and Huperzine A (HuA, 0.1 mg/kg, i.p.) was administered during CIH exposure for 21 days. HuA significantly improved cognitive impairment and neuronal damage in the hippocampus of CIH mice via increasing the ratio of Bcl-2/Bax and inhibiting caspase-3 cleavage. HuA considerably decreased ROS levels by downregulating the high levels of NADPH oxidase (NOX 2, NOX 4) mediated by CIH. There was an overload of iron, which was characterized by high levels of ferritin (FTL and FTH) and transferrin receptor 1 (TfR1) and low levels of ferroportin 1 (FPN1) in the hippocampus of CIH mice. Decreased levels of TfR1 and FTL proteins observed in HuA treated CIH group, could reduce iron overload in hippocampus. HuA increased PSD 95 protein expression, CREB activation and BDNF protein expression to protect against synaptic plasticity impairment induced by CIH. HuA acts as an effective iron chelator to attenuate apoptosis, oxidative stress and synaptic plasticity mediated by CIH.

中文翻译：

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石杉碱甲减少了暴露于慢性间歇性缺氧的小鼠的脑铁负荷，并减轻了其认知缺陷。

慢性间歇性缺氧（CIH）是阻塞性睡眠呼吸暂停（OSA）的结果，它会增加活性氧（ROS）的产生，从而导致氧化损伤和神经认知障碍。本研究旨在确定在CIH条件下大脑中是否发生异常的铁代谢，以及石杉碱甲（HuA）能否改善异常的铁代谢和神经系统损害。通过将吸氧量（FiO2）的百分比从21％降至9％20次/小时，持续8小时/小时来建立CIH小鼠模型，并在CIH期间给予石杉碱A（HuA，0.1 mg / kg，ip）暴露21天。HuA通过增加Bcl-2 / Bax的比例和抑制caspase-3裂解，显着改善CIH小鼠海马的认知障碍和神经元损伤。HuA通过下调CIH介导的高水平NADPH氧化酶（NOX 2，NOX 4）而大大降低了ROS水平。CIH小鼠海马中铁含量过高，其特征是高水平的铁蛋白（FTL和FTH）和转铁蛋白受体1（TfR1）和低水平的铁转运蛋白1（FPN1）。HuA治疗的CIH组中观察到的TfR1和FTL蛋白水平降低，可以减少海马中的铁超载。HuA可增加PSD 95的蛋白表达，CREB激活和BDNF的蛋白表达，从而防止CIH引起的突触可塑性损伤。HuA是有效的铁螯合剂，可减轻CIH介导的细胞凋亡，氧化应激和突触可塑性。其特点是在CIH小鼠的海马中高水平的铁蛋白（FTL和FTH）和转铁蛋白受体1（TfR1）和低水平的铁转运蛋白1（FPN1）。HuA治疗的CIH组中观察到的TfR1和FTL蛋白水平降低，可以减少海马中的铁超载。HuA增加了PSD 95蛋白表达，CREB激活和BDNF蛋白表达，以防止CIH诱导的突触可塑性损伤。HuA是有效的铁螯合剂，可减轻CIH介导的细胞凋亡，氧化应激和突触可塑性。其特点是CIH小鼠海马中的铁蛋白（FTL和FTH）和转铁蛋白受体1（TfR1）含量高，而铁转运蛋白1（FPN1）含量低。HuA治疗的CIH组中观察到的TfR1和FTL蛋白水平降低，可以减少海马中的铁超载。HuA增加了PSD 95蛋白表达，CREB激活和BDNF蛋白表达，以防止CIH诱导的突触可塑性损伤。HuA是有效的铁螯合剂，可减轻CIH介导的细胞凋亡，氧化应激和突触可塑性。CREB激活和BDNF蛋白表达可防止CIH引起的突触可塑性损伤。HuA是有效的铁螯合剂，可减轻CIH介导的细胞凋亡，氧化应激和突触可塑性。CREB激活和BDNF蛋白表达可防止CIH引起的突触可塑性损伤。HuA是有效的铁螯合剂，可减轻CIH介导的细胞凋亡，氧化应激和突触可塑性。