Tianjin Key Laboratory of Radiation Medicine and Molecular Nuclear Medicine, Institute of Radiation Medicine, Chinese Academy of Medical Science, Tianjin 300192, China.
Int J Mol Sci. 2021 Sep 8;22(18):9715. doi: 10.3390/ijms22189715.
Intestinal injury caused by ionizing radiation (IR) is a main clinical issue for patients with cancer receiving abdominal or pelvic radiotherapy. Melatonin (-acetyl-5-methoxytryptamine) is a neurohormone that the pineal gland in the brain normally secretes. The study aimed to disclose the potential function of melatonin in intestinal injury induced by IR and its mechanism. Pretreatment with melatonin enhanced the 30-day survival rate of the irradiated mice and promoted the recovery of the intestinal epithelium and hematopoietic function following abdominal irradiation (ABI). Melatonin altered the gene profile of the small intestines from mice following ABI. The enriched biological process terms for melatonin treatment prior to radiation were mainly involved in the immune process. LPS/IL-1-mediated inhibition of RXR Function, TWEAK signaling, and Toll-like receptor signaling were the most activated canonical pathways targeted by melatonin. An upstream analysis network showed that Tripartite motif-containing 24 (TRIM24) was the most significantly inhibited and S100 calcium binding protein A9 (S100A9) activated. TRIM24 activated atherogenesis and cell viability in breast cancer cell lines and S100A9 inhibited the metabolism of amino acids. Melatonin has radioprotective effects on ABI-caused intestinal injury. The mechanisms behind the beneficial effects of melatonin were involved in activation of the immunity. It is necessary to conduct further experiments to explore the underlying mechanisms.
电离辐射（IR）引起的肠道损伤是接受腹部或骨盆放射治疗的癌症患者的主要临床问题。褪黑素（N-乙酰-5-甲氧基色胺）是大脑松果体正常分泌的神经激素。本研究旨在揭示褪黑素在 IR 诱导的肠道损伤中的潜在功能及其机制。预先用褪黑素处理可提高辐照小鼠的 30 天存活率，并促进腹部照射（ABI）后肠道上皮和造血功能的恢复。褪黑素改变了 ABI 后小鼠小肠的基因谱。辐射前褪黑素处理的富集生物学过程术语主要涉及免疫过程。LPS/IL-1 介导的 RXR 功能、TWEAK 信号和 Toll 样受体信号是褪黑素靶向的最活跃的经典途径。上游分析网络表明，三结构域蛋白 24（TRIM24）被显著抑制，S100 钙结合蛋白 A9（S100A9）被激活。TRIM24 激活了乳腺癌细胞系中的动脉粥样硬化形成和细胞活力，而 S100A9 抑制了氨基酸的代谢。褪黑素对 ABI 引起的肠道损伤具有放射防护作用。褪黑素有益作用的机制涉及免疫激活。有必要进行进一步的实验来探索潜在的机制。
