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基于非靶向代谢组学的急性放射性肠炎大鼠血清代谢轮廓分析

Comprehensive Analysis of Serum Metabolites Profiles in Acute Radiation Enteritis Rats by Untargeted Metabolomics.

机构信息

Department of Gastroenterology, Wuxi People's Hospital Affiliated to Nanjing Medical University.

出版信息

Tohoku J Exp Med. 2021 Nov;255(3):257-265. doi: 10.1620/tjem.255.257.

DOI:10.1620/tjem.255.257
PMID:34853247
Abstract

Acute radiation enteritis is a common complication occurring in patients with pelvic and abdominal tumors who receive radiotherapy. Acute radiation enteritis seriously reduces the life quality, even threatens the lives of patients. Untargeted metabolomics is an emerging strategy to explore the novel biomarkers and uncover potential pathogenesis of acute radiation enteritis. Acute radiation enteritis rat model was established by single abdominal irradiation with a gamma-ray dose of 10 Gy. Serum from 15 acute radiation enteritis rats and 10 controls was extracted for metabolomics analysis by UHPLC-Q-TOF/MS. Clinical manifestations and morphological alterations of intestine confirmed the successful establishment of acute radiation enteritis. According to the metabolomics data, 6,044 positive peaks and 4,241 negative peaks were extracted from each specimen. OPLS-DA analysis and the heat map for cluster analysis showed satisfactory discriminatory power between acute radiation enteritis rats and controls. Subsequent analysis extracted 66 significantly differentially expressed metabolites, which might be potential biomarkers for acute radiation enteritis diagnosis. Moreover, Kyoto Encyclopedia of Genes and Genomes enrichment analyses uncovered the potential mechanisms through which differentially expressed metabolites participated in acute radiation enteritis pathogenesis. To sum up, we summarized several differentially expressed serum metabolites as potential biomarkers for diagnosis of acute radiation enteritis and provide latent clues for elucidating acute radiation enteritis pathology.

摘要

急性放射性肠炎是盆腔和腹部肿瘤患者接受放射治疗后常见的并发症。急性放射性肠炎严重降低了患者的生活质量,甚至威胁患者的生命。非靶向代谢组学是一种新兴的策略,可用于探索新型生物标志物并揭示急性放射性肠炎的潜在发病机制。采用单次腹部γ射线照射(10 Gy)建立急性放射性肠炎大鼠模型。对 15 只急性放射性肠炎大鼠和 10 只对照大鼠的血清进行 UHPLC-Q-TOF/MS 代谢组学分析。临床症状和肠组织形态学改变证实了急性放射性肠炎模型的成功建立。根据代谢组学数据,从每个标本中提取了 6044 个正峰和 4241 个负峰。OPLS-DA 分析和聚类热图显示,急性放射性肠炎大鼠和对照组之间具有良好的区分能力。随后的分析提取了 66 个差异表达代谢物,它们可能是急性放射性肠炎诊断的潜在生物标志物。此外,京都基因与基因组百科全书富集分析揭示了差异表达代谢物参与急性放射性肠炎发病机制的潜在机制。总之,我们总结了几种差异表达的血清代谢物作为急性放射性肠炎诊断的潜在生物标志物,并为阐明急性放射性肠炎的发病机制提供了潜在线索。

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