Abstract

Purpose

Intestinal damage induced by radiation exposure is a major clinic concern of radiotherapy for patients with abdominal or pelvic tumor. Melatonin (N-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).

Materials and methods

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.

Results

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.

Conclusions

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.

中文翻译：

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褪黑激素对γ射线辐射所致小肠损伤小鼠作用的定量蛋白质组学分析

摘要

目的

辐射暴露引起的肠道损伤是腹部或盆腔肿瘤患者放疗的主要临床问题。褪黑激素（N-乙酰-5-甲氧基色胺）可能是一种理想的辐射防护剂，可以保护个人免受辐射暴露。该研究旨在确定褪黑激素在腹部照射 (ABI) 引起的小肠损伤中的作用。

材料和方法

首次检测到 13 Gy ABI 暴露后褪黑激素处理小鼠肠道的 30 天存活率和病理组织学。接下来，检查了小肠组织的定量蛋白质组学分析，并进行了 GO term 和 KEGG 通路分析。

结果

ABI 暴露前褪黑激素治疗显着增加 30 天存活率至 83%，并改善对肠上皮细胞的损伤。褪黑激素显着​​改变了照射后小肠的蛋白质谱。与辐照小鼠相比，用褪黑激素处理的辐照小鼠中，富集的 GO 项主要涉及对其他生物的防御反应（BP，GO：0098542）、对其他生物的反应（BP，GO：0051707）、阴离子跨膜转运蛋白活性（MF，GO：0008509）和次级主动跨膜转运蛋白活性（MF，GO：0015291）。在抗氧化过程中 (MF, GO: 0016209)，辐射前的褪黑激素处理表现出高蛋白质水平的 Sod3 和 Gpx3。辐射前褪黑激素处理的显着 KEGG 途径主要包括蛋白质消化和吸收 (ko 04974) 和矿物质吸收 (ko 04978)。p53 信号通路和 DNA 修复通路在褪黑激素处理的小鼠中富集。在褪黑激素治疗的小鼠中，辐射诱导的 DNA 损伤量和小肠细胞凋亡减少。

结论

褪黑激素可以通过增加 DNA 修复和减少小肠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激素减轻 ABI 引起的肠道损伤提供了前景。