Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, 43 Renmin Avenue, Hainan Province, Haikou 570208, PR China.
Department of Neurosurgery, Haikou Affiliated Hospital of Central South University Xiangya School of Medicine, 43 Renmin Avenue, Hainan Province, Haikou 570208, PR China.
Brain Res. 2024 Dec 15;1845:149219. doi: 10.1016/j.brainres.2024.149219. Epub 2024 Aug 31.
Neuronal cell ferroptosis following intracerebral hemorrhage (ICH) is a crucial factor contributing to the poor prognosis of ICH patients. The objective of this investigation was to investigate the molecular mechanism of IL-1β-induced mesenchymal stem cell-derived exosomes (IL-1β-Exo) in mitigating ICH injury.
Exo and IL-1β-Exo were obtained and identified. Hemin was used to induce an ICH model, and an ICH mouse model was established using Collagenase. Exo and IL-1β-Exo interventions were conducted to study their impact and molecular mechanisms on neuronal ferroptosis in ICH.
Vesicular structure Exo and IL-1β-Exo, with an average particle size of 141.7 ± 38.8 nm and 138.8 ± 37.5 nm, respectively, showed high expression of CD63, CD9 and CD81 could be taken up by SH-SY5Y cells. These Exos reversed Hemin-induced abnormalities in neuronal cells, including elevated iron, Fe, ROS, MDA, 4-HNE, and decreased SOD, GSH-Px, GSH, FTH1 levels, and cell vitality. The RNA content of IL-1β-Exo was linked to its ability to reduce iron accumulation. There was an interaction between HSPA5 and GPX4. Exo and IL-1β-Exo reversed Hemin-induced downregulation of HSPA5 and GPX4 expression. Overexpression and knockdown of HSPA5 respectively potentiate or counteract the impacts of Exo and IL-1β-Exo. IL-1β-Exo was more effective than Exo. These findings were further validated in ICH mice. Moreover, both Exo and IL-1β-Exo reduced the modified neurological severity score and brain water content, as well as alleviated pathological damage in ICH mice.
IL-1β-Exo inhibited neuronal ferroptosis in ICH through the HSPA5/GPX4 axis.
脑出血（ICH）后神经元细胞铁死亡是导致 ICH 患者预后不良的关键因素。本研究旨在探讨白细胞介素 1β（IL-1β）诱导间充质干细胞衍生外泌体（IL-1β-Exo）减轻 ICH 损伤的分子机制。
获取并鉴定 Exo 和 IL-1β-Exo。使用血红素诱导 ICH 模型，胶原酶建立 ICH 小鼠模型。进行 Exo 和 IL-1β-Exo 干预，研究其对 ICH 神经元铁死亡的影响及其分子机制。
Exo 和 IL-1β-Exo 呈囊泡状结构，平均粒径分别为 141.7±38.8nm 和 138.8±37.5nm，均高表达 CD63、CD9 和 CD81，可被 SH-SY5Y 细胞摄取。这些 Exo 逆转了血红素诱导的神经元细胞异常，包括铁、Fe、ROS、MDA、4-HNE 升高，SOD、GSH-Px、GSH、FTH1 水平降低，细胞活力下降。IL-1β-Exo 的 RNA 含量与其减少铁积累的能力相关。HSPA5 与 GPX4 之间存在相互作用。Exo 和 IL-1β-Exo 逆转了血红素诱导的 HSPA5 和 GPX4 表达下调。HSPA5 的过表达和敲低分别增强或拮抗 Exo 和 IL-1β-Exo 的作用。IL-1β-Exo 比 Exo 更有效。这些发现在 ICH 小鼠中得到了进一步验证。此外，Exo 和 IL-1β-Exo 均降低了改良神经功能缺损评分和脑含水量，减轻了 ICH 小鼠的病理损伤。
IL-1β-Exo 通过 HSPA5/GPX4 轴抑制 ICH 中的神经元铁死亡。
