Zhao Ying-Yong, Chen Hua, Tian Ting, Chen Dan-Qian, Bai Xu, Wei Feng
Key Laboratory of Resource Biology and Biotechnology in Western China, Ministry of Education, The College of Life Sciences, Northwest University, Xi'an, China.
Solution Centre, Waters Technologies (Shanghai) Ltd., Shanghai, China.
PLoS One. 2014 Dec 23;9(12):e115467. doi: 10.1371/journal.pone.0115467. eCollection 2014.
Chronic kidney disease (CKD) is an important public health problem. Ergone has been proved to prevent the progression of CKD. UPLC-QTOF/HDMS was employed for metabolic profiling of adenine-induced CKD and to investigate the nephroprotective effects of ergone. Pharmacology parameters including blood biochemistry, histopathological evaluation and Western blot analysis were performed concurrently. The UPLC-MS data were analyzed by partial least squares-discriminate analysis, correlation analysis, heatmap analysis and mapped to KEGG pathways. Blood and serum biochemistry were observed to be significantly different in the CKD group than in the control group. In conjunction with biochemistry, histopathology and protein expression results, identified metabolites indicated perturbations in fatty acid metabolism, purine metabolism and amino acid metabolism as changes associated with adenine-induced CKD and the interventions of ergone. Upregulated expression of TGF-β1, ED-1, CTGF, bFGF and collagen I was observed in the CKD group. However, downregulated expression of these proteins was observed after oral administration of ergone. These results suggest that expression changes in these proteins had implications for fatty acid metabolism, purine metabolism and amino acid metabolism in the development of CKD and that ergone treatment could delay the development of CKD by normalizing or blocking abnormal changes in biomarker metabolites and protein expression in the CKD group.
慢性肾脏病（CKD）是一个重要的公共卫生问题。已证实麦角硫因可预防CKD的进展。采用超高效液相色谱-四极杆飞行时间/高分辨质谱联用技术（UPLC-QTOF/HDMS）对腺嘌呤诱导的CKD进行代谢谱分析，并研究麦角硫因的肾保护作用。同时进行包括血液生化、组织病理学评估和蛋白质印迹分析在内的药理学参数检测。通过偏最小二乘判别分析、相关性分析、热图分析对UPLC-MS数据进行分析，并将其映射到KEGG通路。观察到CKD组的血液和血清生化指标与对照组有显著差异。结合生化、组织病理学和蛋白质表达结果，鉴定出的代谢物表明脂肪酸代谢、嘌呤代谢和氨基酸代谢紊乱是与腺嘌呤诱导的CKD及麦角硫因干预相关的变化。在CKD组中观察到转化生长因子-β1（TGF-β1）、ED-1、结缔组织生长因子（CTGF）、碱性成纤维细胞生长因子（bFGF）和I型胶原蛋白的表达上调。然而，口服麦角硫因后这些蛋白质的表达下调。这些结果表明，这些蛋白质的表达变化在CKD的发生发展中对脂肪酸代谢、嘌呤代谢和氨基酸代谢有影响，并且麦角硫因治疗可通过使CKD组生物标志物代谢物和蛋白质表达的异常变化正常化或阻断这些变化来延缓CKD的发展。
