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. 2021;97(9):1206-1216. doi: 10.1080/09553002.2021.1956006. Epub 2021 Jul 29.
Intestinal damage induced by radiation exposure is a major clinic concern of radiotherapy for patients with abdominal or pelvic tumor. Melatonin (-acetyl-5-methoxytryptamine) is likely be an ideal radioprotector to protect individuals from radiation exposure. The study aimed to define the role of melatonin in small intestinal damage caused by abdominal irradiation (ABI).
30-day survival rate and pathological histology of the intestines from melatonin-treated mice after 13 Gy ABI exposure was first detected. Next, quantitative proteomics analysis of the small intestines tissue was examined and GO term and KEGG pathways analysis were performed.
Melatonin treatment before ABI exposure significantly increased 30-day survival rate to 83% and ameliorated damage to the intestinal epithelial cells. Melatonin significantly altered the proteins profile of the small intestines following irradiation. For the irradiated mice treated with melatonin in comparison with the irradiated mice, the enriched GO terms were mainly involved in defense response to other organism (BP, GO: 0098542), response to other organism (BP, GO: 0051707), anion transmembrane transporter activity (MF, GO: 0008509), and secondary active transmembrane transporter activity (MF, GO: 0015291). In the process of antioxidant activity (MF, GO: 0016209), melatonin treatment prior to radiation exhibited high protein levels of Sod3 and Gpx3. The markedly KEGG pathways for melatonin treatment prior to radiation mainly included protein digestion and absorption (ko 04974) and mineral absorption (ko 04978). p53 signaling pathway and DNA repair pathways were enriched in melatonin treated mice. The amount of radiation-induced DNA damage and the cell apoptosis of the small intestines was decreased in the melatonin-treated mice.
Melatonin may protect small intestines from radiation damage through increasing DNA repair and decreasing cell apoptosis of the small intestines. Our data provided perspective for the study of melatonin in mitigating ABI-caused intestinal damage.
辐射暴露引起的肠道损伤是腹部或骨盆肿瘤患者放射治疗的主要临床关注点。褪黑素(N-乙酰-5-甲氧基色胺)可能是一种理想的辐射防护剂,可以保护个体免受辐射暴露。本研究旨在确定褪黑素在腹部照射(ABI)引起的小肠损伤中的作用。
首先检测了 13Gy ABI 照射后接受褪黑素治疗的小鼠的 30 天存活率和肠道病理组织学。接下来,对小肠组织进行了定量蛋白质组学分析,并进行了 GO 术语和 KEGG 途径分析。
ABI 暴露前给予褪黑素治疗可显著提高 30 天存活率至 83%,并改善肠上皮细胞损伤。褪黑素照射后显著改变了小肠的蛋白质谱。与照射小鼠相比,用褪黑素处理的照射小鼠中富集的 GO 术语主要涉及对其他生物体的防御反应(BP,GO:0098542)、对其他生物体的反应(BP,GO:0051707)、阴离子跨膜转运体活性(MF,GO:0008509)和继发性主动跨膜转运体活性(MF,GO:0015291)。在抗氧化活性过程中(MF,GO:0016209),褪黑素治疗在辐射前表现出 Sod3 和 Gpx3 的高蛋白水平。褪黑素治疗前的显著 KEGG 途径主要包括蛋白质消化吸收(ko04974)和矿物质吸收(ko04978)。p53 信号通路和 DNA 修复途径在褪黑素处理的小鼠中富集。褪黑素处理的小鼠中小肠的辐射诱导 DNA 损伤量和细胞凋亡减少。
褪黑素通过增加小肠的 DNA 修复和减少细胞凋亡来保护小肠免受辐射损伤。我们的数据为研究褪黑素减轻 ABI 引起的肠道损伤提供了新视角。