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药物诱导急性肾损伤大鼠模型尿液来源细胞外囊泡的代谢组学分析。

Metabolomic profiling of urine-derived extracellular vesicles from rat model of drug-induced acute kidney injury.

机构信息

DMPK Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa, 227-0033, Japan; Laboratory of Analytical and Bio-Analytical Chemistry, School of Pharmaceutical Sciences, University of Shizuoka, 52-1 Yada, Suruga-ku, Shizuoka, 422-8526, Japan.

DMPK Research Laboratories, Mitsubishi Tanabe Pharma Corporation, Yokohama, Kanagawa, 227-0033, Japan.

出版信息

Biochem Biophys Res Commun. 2021 Mar 26;546:103-110. doi: 10.1016/j.bbrc.2021.01.082. Epub 2021 Feb 10.

Abstract

Extracellular vesicles (EVs) are lipid bilayer particles that are released by various cells and provide a real-time snapshot of the state of these cells in tissue in a noninvasive manner. EVs contain components, including mRNA, miRNAs, proteins, and metabolites. Therefore, EVs hold promise for the discovery of liquid biopsy-based biomarkers for disease diagnosis. In the present study, metabolome analysis of urine EVs in rats with kidney injury caused by cisplatin and puromycin aminonucleoside was performed using liquid chromatography/mass spectrometry to identify candidate biomarkers that reflect the type and extent of injury in drug-induced nephrotoxicity. A total of 396 metabolites were detected in urine EVs, of which 65 were identified as potential biomarkers in urine EVs of drug-induced nephrotoxicity. Pathway analysis revealed that these metabolites may reflect changes occurring within damaged cells during kidney injury, suggesting that metabolomics of urine EVs could be a useful informative tool.

摘要

细胞外囊泡 (EVs) 是由各种细胞释放的脂质双层颗粒,以非侵入性的方式提供组织中这些细胞状态的实时快照。EVs 包含包括 mRNA、miRNAs、蛋白质和代谢物在内的成分。因此,EVs 有望发现基于液体活检的疾病诊断生物标志物。在本研究中,使用液相色谱/质谱法对顺铂和嘌呤霉素氨基核苷引起的肾损伤大鼠的尿 EVs 进行代谢组学分析,以鉴定反映药物诱导肾毒性中损伤类型和程度的候选生物标志物。在尿 EVs 中检测到 396 种代谢物,其中 65 种被鉴定为药物诱导肾毒性尿 EVs 中的潜在生物标志物。途径分析表明,这些代谢物可能反映了肾损伤过程中受损细胞内发生的变化,这表明尿 EVs 的代谢组学可能是一种有用的信息工具。

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