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采用超高效液相色谱-串联四极杆飞行时间质谱法(UPLC-Q/TOF-MS)发现急性肾损伤的潜在生物标志物。

Discovery of potential biomarkers in acute kidney injury by ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS).

机构信息

Department of Nephrology, Anhui Provincial Hospital Affiliated With Anhui Medical University, 17 Lujiang Road, Luyang, Hefei, 230001, Anhui, China.

State Key Laboratory of Tea Tree Biology and Resource Utilization, Anhui Agricultural University, 130 West Changjiang Road, Shushan, Hefei, 230036, Anhui, China.

出版信息

Int Urol Nephrol. 2021 Dec;53(12):2635-2643. doi: 10.1007/s11255-021-02829-3. Epub 2021 Mar 8.

Abstract

OBJECTIVE

The LC-MS/MS-based non-targeted metabolomics method was used to differentially screen serum and urine metabolites of acute kidney injury (AKI) patients and healthy people, to explore potential biomarkers of AKI and analyze related pathways, and explain the potential mechanism and biological significance of AKI.

METHODS

The serum and urine samples from 30 AKI patients and 20 healthy people were selected to conduct a non-targeted metabolomics study by ultra-high-performance liquid chromatography-tandem quadrupole time-of-flight mass spectrometry (UPLC-Q/TOF-MS). The differential metabolites between the two groups were searched by the human metabolome (HMDB) database ( https://hmdb.ca/ ) and the related pathways of these potential biomarkers were identified by searching the Kyoto encyclopedia of genes and genomes (KEGG) database ( https://www.kegg.jp/ ). The total metabolic pathways were analyzed by the MS Peaks to Pathways module of MetaboAnalyst ( https://www.metaboanalyst.ca/ ).

RESULTS

Multivariate data analysis found that serum and urine metabolism in AKI patients was significantly different from healthy people. We found three metabolites in urine (2-S-glutathionyl glutathione acetate, 5-L-Glutamyl-taurine, and L-Phosphoarginine) contributing to the separation of AKI patients from healthy people, and major metabolic pathways associated with these potential biomarkers including cytochrome P450 metabolism, arginine, and proline metabolism.

CONCLUSION

2-S-glutathionyl glutathione acetate, 5-L-Glutamyl-taurine, and L-Phosphoarginine were associated with AKI patients, which could be selected as potential biomarkers to predicate AKI disease.

摘要

目的

采用基于 LC-MS/MS 的非靶向代谢组学方法,对急性肾损伤(AKI)患者和健康人群的血清和尿液代谢物进行差异筛选,探讨 AKI 的潜在生物标志物,分析相关通路,并解释 AKI 的潜在机制和生物学意义。

方法

选取 30 例 AKI 患者和 20 例健康人血清和尿液样本,采用超高效液相色谱-串联四极杆飞行时间质谱法(UPLC-Q/TOF-MS)进行非靶向代谢组学研究。通过人代谢组数据库(HMDB)(https://hmdb.ca/)搜索两组间的差异代谢物,并通过京都基因与基因组百科全书(KEGG)数据库(https://www.kegg.jp/)搜索这些潜在生物标志物的相关通路。通过 MetaboAnalyst 中的 MS Peaks to Pathways 模块对总代谢通路进行分析。

结果

多变量数据分析发现,AKI 患者的血清和尿液代谢明显不同于健康人。我们在尿液中发现了三个与 AKI 患者区分开的代谢物(2-S-谷胱甘肽半胱氨酸乙酸酯、5-L-谷氨酰牛磺酸和 L-磷酸精氨酸),与这些潜在生物标志物相关的主要代谢途径包括细胞色素 P450 代谢、精氨酸和脯氨酸代谢。

结论

2-S-谷胱甘肽半胱氨酸乙酸酯、5-L-谷氨酰牛磺酸和 L-磷酸精氨酸与 AKI 患者相关,可作为预测 AKI 疾病的潜在生物标志物。

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