Li Wanyi, Liu Xiaoqing, Li Honglin, Zeng Jiawei, Chen Yan, Xu Bei
Department of Clinical Laboratory, School of Medicine, Mianyang Central Hospital, University of Electronic Science and Technology of China, Mianyang, 621000, Sichuan, China.
Department of Pharmacy, Sichuan Clinical Research Center for Cancer, Sichuan Cancer Center, Sichuan Cancer Hospital & Institute, University of Electronic Science and Technology of China, Chengdu, 610000, Sichuan, China.
Sci Rep. 2024 Dec 3;14(1):30101. doi: 10.1038/s41598-024-81600-x.
Renal ischemia-reperfusion injury (IRI) is an important cause of acute kidney injury (AKI). However, the pathophysiological changes and mechanisms during IRI-AKI progression remain unclear. This study aims toinvestigate the potential mechanisms in the progression of IRI-AKI by integrating metabolomics and transcriptomics data, providing a reference for the subsequent identification of biomarkers and therapeutic targets. IRI-AKI rat models with 30 min of ischemia and 24-72 h of reperfusion surgery simulating the progression of AKI were established. Compared to the control group underwent sham surgery (NC group), most of the differentially expressed metabolites (DEMs) in IRI-AKI 24 h and IRI-AKI 72 h decreased, mainly including amino acids, organic acids, and carnitines. Additionally, we found that DEMs were mainly enriched in amino acid-related pathways, among which valine, leucine, and isoleucine biosynthesis were dramatically altered in all comparisons. Transcriptomics revealed that differentially expressed genes (DEGs) were primarily involved in amino acid, lipid, and fatty acid metabolism. By integrating metabolomics and transcriptomics, we found valine, leucine, and isoleucine biosynthesis play key roles in IRI-AKI development. Our findings concluded that valine, leucine, and isoleucine pathways are hubs that potentially connect transcriptomes to metabolomes, providing new insights regarding the pathogenesis of IRI-AKI and its potential biomarkers and therapeutic strategies.
肾缺血再灌注损伤（IRI）是急性肾损伤（AKI）的重要原因。然而，IRI-AKI进展过程中的病理生理变化和机制仍不清楚。本研究旨在通过整合代谢组学和转录组学数据，探讨IRI-AKI进展中的潜在机制，为后续生物标志物的鉴定和治疗靶点提供参考。建立了模拟AKI进展的缺血30分钟和再灌注手术24-72小时的IRI-AKI大鼠模型。与接受假手术的对照组（NC组）相比，IRI-AKI 24小时和IRI-AKI 72小时中大多数差异表达代谢物（DEM）减少，主要包括氨基酸、有机酸和肉碱。此外，我们发现DEM主要富集在氨基酸相关途径中，其中缬氨酸、亮氨酸和异亮氨酸的生物合成在所有比较中均发生了显著变化。转录组学显示差异表达基因（DEG）主要参与氨基酸、脂质和脂肪酸代谢。通过整合代谢组学和转录组学，我们发现缬氨酸、亮氨酸和异亮氨酸的生物合成在IRI-AKI发展中起关键作用。我们的研究结果得出结论，缬氨酸、亮氨酸和异亮氨酸途径是潜在连接转录组和代谢组的枢纽，为IRI-AKI的发病机制及其潜在生物标志物和治疗策略提供了新的见解。
