Second Clinical Medical College, Guangzhou University of Chinese Medicine, Guangzhou, P.R. China.
Department of Neurology, Affiliated Jiangmen Traditional Chinese Medicine Hospital of Ji'nan University, Jiangmen, P.R. China.
ASN Neuro. 2021 Jan-Dec;13:17590914211010647. doi: 10.1177/17590914211010647.
Intracerebral haemorrhage (ICH) is a devastating subtype of stroke with high morbidity and mortality. It has been reported that paeonol (PAN) inhibits the progression of ICH. However, the mechanism by which paeonol mediates the progression of ICH remains unclear. To mimic ICH , neuronal cells were treated with hemin. An model of ICH was established to detect the effect of paeonol on ferroptosis in neurons during ICH. Cell viability was tested by MTT assay. Furthermore, cell injury was detected by GSH, MDA and ROS assays. Ferroptosis was examined by iron assay. RT-qPCR and western blotting were used to detect gene and protein expression, respectively. The correlation among HOTAIR, UPF1 and ACSL4 was explored by FISH, RNA pull-down and RIP assays. Paeonol significantly inhibited the ferroptosis of neurons in ICH mice. In addition, paeonol significantly reversed hemin-induced injury and ferroptosis in neurons, while this phenomenon was notably reversed by HOTAIR overexpression. Moreover, paeonol notably inhibited ferroptosis in hemin-treated neuronal cells via inhibition of ACSL4. Additionally, HOTAIR bound to UPF1, and UPF1 promoted the degradation of ACSL4 by binding to ACSL4. Furthermore, HOTAIR overexpression reversed paeonol-induced inhibition of ferroptosis by mediating the UPF1/ACSL4 axis. Paeonol inhibits the progression of ICH by mediating the HOTAIR/UPF1/ACSL4 axis. Therefore, paeonol might serve as a new agent for the treatment of ICH.
脑出血（ICH）是一种具有高发病率和死亡率的破坏性中风亚型。据报道，丹皮酚（PAN）抑制 ICH 的进展。然而，丹皮酚介导 ICH 进展的机制尚不清楚。为了模拟 ICH，用血红素处理神经元细胞。建立 ICH 模型，以检测丹皮酚对 ICH 期间神经元中铁死亡的影响。通过 MTT 测定法检测细胞活力。此外，通过 GSH、MDA 和 ROS 测定法检测细胞损伤。通过铁测定法检测铁死亡。使用 RT-qPCR 和 Western blot 分别检测基因和蛋白表达。通过 FISH、RNA 下拉和 RIP 测定法探索 HOTAIR、UPF1 和 ACSL4 之间的相关性。丹皮酚显著抑制 ICH 小鼠神经元中的铁死亡。此外，丹皮酚显著逆转了血红素诱导的神经元损伤和铁死亡，而 HOTAIR 过表达明显逆转了这种现象。此外，丹皮酚通过抑制 ACSL4 显著抑制血红素处理的神经元细胞中的铁死亡。此外，HOTAIR 与 UPF1 结合，UPF1 通过与 ACSL4 结合促进 ACSL4 的降解。此外，HOTAIR 过表达通过介导 UPF1/ACSL4 轴逆转了丹皮酚诱导的铁死亡抑制。丹皮酚通过介导 HOTAIR/UPF1/ACSL4 轴抑制 ICH 的进展。因此，丹皮酚可能成为治疗 ICH 的一种新药物。
