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基于非靶向代谢组学对小鼠肺上皮细胞辐射诱导的代谢改变的探索

[Non-targeted Metabolomics-based Exploration of
Radiation-induced Metabolic Alterations in Mouse Lung Epithelial Cells].

作者信息

Fan Hao, Ge Xiangwei, Zhou Xin, Li Yao, Liu Qiaowei, Hu Yi

机构信息

Chinese PLA Medical School, Beijing 100853, China.

Department of Oncology, the Fifth Medical Center,
Chinese PLA General Hospital, Beijing 100071, China.

出版信息

Zhongguo Fei Ai Za Zhi. 2024 Oct 20;27(10):725-734. doi: 10.3779/j.issn.1009-3419.2024.106.28.

DOI:10.3779/j.issn.1009-3419.2024.106.28
PMID:39631829
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC11629006/
Abstract

BACKGROUND

Metabolic change is one of the important characteristics of radiation pneumonitis. Radiotherapy, as a conventional method for the treatment of thoracic tumors, can not only effectively kill tumor cells, but also cause adverse reactions such as local inflammation and fibrosis, which leads to limited therapeutic effect and profound impact on the quality of life of patients. Therefore, it is of great significance to explore the metabolic changes caused by radiotherapy. The aim of this study was to investigate the effects of X-ray irradiation on the metabolism of a mouse lung epithelial cell line (murine lung epithelial-12, MLE12).

METHODS

MLE12 cells were' cultured in vitro and randomly divided into radiation group (IR) and control group (NC). Cells in the IR group were irradiated at a dose of 10 Gy using a Hitachi X-ray irradiator. Cell supernatant samples were collected at 48 h after irradiation. Metabolomic analysis of the samples was performed by liquid chromatograph mass spectrometer (LC/MS).

RESULTS

LC/MS metabolomics analysis revealed the metabolic changes of MLE12 cells at 48 h after irradiation. A total of 38 secretory metabolites were altered in the IR group compared with the NC group. According to the annotation of Kyoto Encyclopedia of Genes and Genomes (KEGG) database, the differential metabolites are mainly involved in nucleotide metabolism, amino acid metabolism and lipid metabolism, among which the difference in nucleotide metabolism is the most significant.

CONCLUSIONS

The metabolism of MLE12 cells was significantly affected by X-ray irradiation, mainly affecting the nucleotide metabolic pathways, including purine and pyrimidine metabolites and related metabolic pathways.

摘要

背景

代谢变化是放射性肺炎的重要特征之一。放射治疗作为胸部肿瘤的传统治疗方法,不仅能有效杀死肿瘤细胞,还会引起局部炎症和纤维化等不良反应,导致治疗效果受限,并对患者生活质量产生深远影响。因此,探索放射治疗引起的代谢变化具有重要意义。本研究旨在探讨X射线照射对小鼠肺上皮细胞系(小鼠肺上皮-12,MLE12)代谢的影响。

方法

体外培养MLE12细胞,随机分为辐射组(IR)和对照组(NC)。使用日立X射线照射仪以10 Gy的剂量对IR组细胞进行照射。照射后48小时收集细胞上清液样本。通过液相色谱-质谱联用仪(LC/MS)对样本进行代谢组学分析。

结果

LC/MS代谢组学分析揭示了照射后48小时MLE12细胞的代谢变化。与NC组相比,IR组共有38种分泌性代谢产物发生改变。根据京都基因与基因组百科全书(KEGG)数据库的注释,差异代谢产物主要涉及核苷酸代谢、氨基酸代谢和脂质代谢,其中核苷酸代谢的差异最为显著。

结论

X射线照射显著影响了MLE12细胞的代谢,主要影响核苷酸代谢途径,包括嘌呤和嘧啶代谢产物及相关代谢途径。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/93164e809891/zgfazz-27-10-725-img_5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/ad9f7f0838a1/zgfazz-27-10-725-img_1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/536476cbf003/zgfazz-27-10-725-img_2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/5e7da4a94ee8/zgfazz-27-10-725-img_3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/2cfc8bb1e77e/zgfazz-27-10-725-img_4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/93164e809891/zgfazz-27-10-725-img_5.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/ad9f7f0838a1/zgfazz-27-10-725-img_1.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/536476cbf003/zgfazz-27-10-725-img_2.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/5e7da4a94ee8/zgfazz-27-10-725-img_3.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/2cfc8bb1e77e/zgfazz-27-10-725-img_4.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/1a86/11629006/93164e809891/zgfazz-27-10-725-img_5.jpg

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