Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science and Peking Union Medical College, Tianjin, China.
Int J Radiat Biol. 2023;99(10):1607-1618. doi: 10.1080/09553002.2023.2194399. Epub 2023 Mar 31.
Intestinal injuries caused by ionizing radiation (IR) are a major complication of radiotherapy. Ferrostatin-1 (Fer-1) exerts antioxidant and anti-inflammatory effects. We investigated the influence of Fer-1 on IR-induced intestinal damage and explored the possible mechanisms.
IEC-6 cells were administrated with Fer-1 for 30 min and subsequently subjected to 9.0 Gy-irradiation. Flow cytometry, qPCR, and WB were used to detect changes. For in vivo experiments, Fer-1 was given intraperitoneally to mice at 1 h before and 24 h after 9.0 Gy total body irradiation (TBI) respectively. Three days after TBI, the small intestines were isolated for analysis. The diversity and composition of the gut microbiota were analyzed by 16S rRNA gene sequencing.
In vitro, Fer-1 protected IEC-6 cells from IR injury by reducing the production of ROS and inhibiting both ferroptosis and apoptosis. In vivo, Fer-1 enhanced the survival rates of mice subjected to lethal doses of IR and restored intestinal structure and physiological function. Further investigation showed that Fer-1 protected IEC-6 cells and mice by inhibiting the p53-mediated apoptosis signaling pathway and restoring the gut-microbe balance.
This study confirms that Fer-1 protects intestinal injuries through suppressing apoptosis and ferroptosis.
电离辐射（IR）引起的肠道损伤是放疗的主要并发症。铁抑素-1（Fer-1）具有抗氧化和抗炎作用。本研究旨在探讨 Fer-1 对 IR 诱导的肠道损伤的影响及其可能的机制。
IEC-6 细胞用 Fer-1 处理 30min 后，再用 9.0Gy 射线照射。采用流式细胞术、qPCR 和 WB 检测变化。在体内实验中，Fer-1 在 9.0Gy 全身照射（TBI）前 1h 和后 24h 分别腹腔注射给予小鼠。TBI 后 3 天，分离小肠进行分析。采用 16S rRNA 基因测序分析肠道微生物群落的多样性和组成。
在体外，Fer-1 通过减少 ROS 的产生和抑制铁死亡和细胞凋亡来保护 IEC-6 细胞免受 IR 损伤。在体内，Fer-1 提高了致命剂量 IR 照射小鼠的存活率，并恢复了肠道结构和生理功能。进一步研究表明，Fer-1 通过抑制 p53 介导的细胞凋亡信号通路和恢复肠道微生物平衡来保护 IEC-6 细胞和小鼠。
本研究证实 Fer-1 通过抑制细胞凋亡和铁死亡来保护肠道损伤。
