Department of Chemistry, Stanford University, Stanford, CA, 94305, USA.
Department of Chemistry, Indian Institute of Science Education and Research Tirupati, Tirupati, 517507, India.
Sci Rep. 2019 Jul 29;9(1):11007. doi: 10.1038/s41598-019-47396-x.
Desorption electrospray ionization mass spectrometry (DESI-MS) is an emerging analytical tool for rapid in situ assessment of metabolomic profiles on tissue sections without tissue pretreatment or labeling. We applied DESI-MS to identify candidate metabolic biomarkers associated with kidney injury at the early stage. DESI-MS was performed on sections of kidneys from 80 mice over a time course following unilateral ureteral obstruction (UUO) and compared to sham controls. A predictive model of renal damage was constructed using the LASSO (least absolute shrinkage and selection operator) method. Levels of lipid and small metabolites were significantly altered and glycerophospholipids comprised a significant fraction of altered species. These changes correlate with altered expression of lipid metabolic genes, with most genes showing decreased expression. However, rapid upregulation of PG(22:6/22:6) level appeared to be a hitherto unknown feature of the metabolic shift observed in UUO. Using LASSO and SAM (significance analysis of microarrays), we identified a set of well-measured metabolites that accurately predicted UUO-induced renal damage that was detectable by 12 h after UUO, prior to apparent histological changes. Thus, DESI-MS could serve as a useful adjunct to histology in identifying renal damage and demonstrates early and broad changes in membrane associated lipids.
解吸电喷雾电离质谱（DESI-MS）是一种新兴的分析工具，可用于快速原位评估组织切片中的代谢组学特征，而无需对组织进行预处理或标记。我们应用 DESI-MS 来鉴定与早期肾损伤相关的候选代谢生物标志物。在单侧输尿管梗阻（UUO）后，对 80 只小鼠的肾脏切片进行 DESI-MS 分析，并与假手术对照进行比较。使用 LASSO（最小绝对收缩和选择算子）方法构建了肾脏损伤的预测模型。脂质和小分子代谢物的水平显著改变，甘油磷脂构成了显著改变的物种的一部分。这些变化与脂质代谢基因表达的改变相关，大多数基因表达下调。然而，PG（22:6/22:6）水平的快速上调似乎是 UUO 观察到的代谢变化中一个未知的特征。使用 LASSO 和 SAM（微阵列的显著性分析），我们确定了一组经过良好测量的代谢物，这些代谢物可以准确预测 UUO 诱导的肾损伤，在 UUO 后 12 小时即可检测到，此时尚无明显的组织学变化。因此，DESI-MS 可以作为组织学的有用补充，用于识别肾损伤，并显示与膜相关的脂质的早期和广泛变化。
