Liu Xin, Tao Xuwei, Xiong Zhen, Wang Huizhen, Zeng Linkong
Department of Neonatal, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Department of Child Healthcare, Wuhan Children's Hospital, Tongji Medical College, Huazhong University of Science & Technology, Wuhan, China.
Brain Inj. 2025;39(8):635-645. doi: 10.1080/02699052.2025.2468309. Epub 2025 Mar 10.
We investigated the mechanism of histone deacetylase 2 (HDAC2) modulating nuclear factor erythroid 2-related factor 2 (Nrf2) acetylation level in neuronal ferroptosis of hypoxic-ischemic brain injury (HIBI) neonatal rats.
The pathological damage and neuronal injury in the hippocampal CA1 region of HIBI neonatal rat models were assessed by HE and Nissl staining. Levels of neuron-specific enolase (NSE), glutathione peroxidase 4 (GPX4), HDAC2, Nrf2, glutathione (GSH), reactive oxygen species (ROS), malondialdehyde (MDA), active Fe, Nrf2 acetylation, and nuclear Nrf2 in hippocampal tissues were determined.
HIBI induced upregulation of HDAC2 expression, causing hippocampal neuronal ferroptosis in neonatal rats, as evidenced by dissolved hippocampal CA1 region, neuronatrophy, reduced number of neurons, abated NSE and GPX4 levels, decreased NeuN+/GPX4+ cells, diminished GSH level, and increased levels of ROS, MDA and active Fe. Inhibition of HDAC2 partially ameliorated neuronal ferroptosis in HIBI neonatal rats. HDAC2 regulated Nrf2 expression and repressed Nrf2 nuclear translocation by mediating Nrf2 deacetylation. Inhibition of Nrf2 partially reversed the ameliorative effect of HDAC2 on neuronal ferroptosis in HIBI neonatal rats.
HDAC2 modulated neuronal ferroptosis in HIBI neonatal rats by mediating Nrf2 deacetylation.
我们研究了组蛋白去乙酰化酶2（HDAC2）调节新生缺氧缺血性脑损伤（HIBI）大鼠神经元铁死亡中核因子红细胞2相关因子2（Nrf2）乙酰化水平的机制。
通过苏木精-伊红（HE）染色和尼氏染色评估HIBI新生大鼠模型海马CA1区的病理损伤和神经元损伤。测定海马组织中神经元特异性烯醇化酶（NSE）、谷胱甘肽过氧化物酶4（GPX4）、HDAC2、Nrf2、谷胱甘肽（GSH）、活性氧（ROS）、丙二醛（MDA）、活性铁、Nrf2乙酰化水平和核Nrf2水平。
HIBI诱导HDAC2表达上调，导致新生大鼠海马神经元铁死亡，表现为海马CA1区溶解、神经元萎缩、神经元数量减少、NSE和GPX4水平降低、NeuN+/GPX4+细胞减少、GSH水平降低以及ROS、MDA和活性铁水平升高。抑制HDAC2可部分改善HIBI新生大鼠的神经元铁死亡。HDAC通过介导Nrf2去乙酰化来调节Nrf2表达并抑制Nrf2核转位。抑制Nrf2可部分逆转HDAC2对HIBI新生大鼠神经元铁死亡的改善作用。
HDAC2通过介导Nrf2去乙酰化调节HIBI新生大鼠的神经元铁死亡。
