Zhou Yuanyu, Wang Yuebin, Wu Xiaoqing, Wu Junjie, Yan Jianhui, Su Wei
Department of Pediatrics, Affiliated Hospital of Xiangnan University, Chenzhou, 423000, Hunan, China.
Clinical College of Xiangnan University, Affiliated Hospital of Xiangnan University, Chenzhou, 423000, Hunan, China.
Transl Neurosci. 2023 Dec 31;14(1):20220331. doi: 10.1515/tnsci-2022-0331. eCollection 2023 Jan 1.
Hypoxic-ischemic encephalopathy (HIE) is a common neurological disorder characterized by ischemia and hypoxia in the perinatal period, which seriously affects the growth and development of newborns. To date, there is no specific drug for the treatment of HIE. Previous studies have shown that ferroptosis plays an important role in the pathogenesis of HIE. Carthamin yellow (CY) is believed to have antioxidant and anti-inflammatory effects. However, no studies have reported the role of CY in ferroptosis in HIE until now. The aim of this study was to investigate the effect and mechanism of CY on HIE and to provide an experimental basis for the clinical treatment of HIE. The results demonstrated that CY increased the expression of NeuN in the neonatal rat hypoxic-ischemic brain damage (HIBD) model. Further exploration revealed that CY increased the expression of glutathione peroxidase 4 and ferritin heavy chain 1 while it decreased the expression of PTGS2 and ACSL2. Moreover, CY decreased malondialdehyde expression and increased superoxide dismutase and glutathione expression . The findings also indicated that CY downregulated the expression of Nrf2 and Keap-1. In conclusion, this study demonstrated that CY attenuated brain injury in an experimental HIBD model, potentially by alleviating hippocampal neuronal ferroptosis through inhibition of the Nrf2/Keap-1 signaling pathway. These findings provide a novel therapeutic strategy for the clinical treatment of HIE.
缺氧缺血性脑病（HIE）是一种常见的神经系统疾病，其特征是围生期缺血缺氧，严重影响新生儿的生长发育。迄今为止，尚无治疗HIE的特效药物。先前的研究表明，铁死亡在HIE的发病机制中起重要作用。红花黄色素（CY）被认为具有抗氧化和抗炎作用。然而，迄今为止，尚无研究报道CY在HIE铁死亡中的作用。本研究的目的是探讨CY对HIE的作用及其机制，为HIE的临床治疗提供实验依据。结果表明，CY可增加新生大鼠缺氧缺血性脑损伤（HIBD）模型中NeuN的表达。进一步研究发现，CY可增加谷胱甘肽过氧化物酶4和铁蛋白重链1的表达，同时降低PTGS2和ACSL2的表达。此外，CY可降低丙二醛表达，增加超氧化物歧化酶和谷胱甘肽表达。研究结果还表明，CY可下调Nrf2和Keap-1的表达。总之，本研究表明，CY可减轻实验性HIBD模型中的脑损伤，可能是通过抑制Nrf2/Keap-1信号通路减轻海马神经元铁死亡。这些发现为HIE的临床治疗提供了一种新的治疗策略。
