Wang Zhonghua, Fu Wenqing, Huo Meiling, He Bingshu, Liu Yaqi, Tian Lu, Li Wanfang, Zhou Zhi, Wang Baili, Xia Jianzhen, Chen Yanhua, Wei Jinfeng, Abliz Zeper
Key Laboratory of Mass Spectrometry Imaging and Metabolomics (Minzu University of China), National Ethnic Affairs Commission, Beijing 100081, China.
College of Life and Environmental Sciences, Minzu University of China, Beijing 100081, China.
Acta Pharm Sin B. 2021 Nov;11(11):3665-3677. doi: 10.1016/j.apsb.2021.05.013. Epub 2021 May 20.
Detailed knowledge on tissue-specific metabolic reprogramming in diabetic nephropathy (DN) is vital for more accurate understanding the molecular pathological signature and developing novel therapeutic strategies. In the present study, a spatial-resolved metabolomics approach based on air flow-assisted desorption electrospray ionization (AFADESI) and matrix-assisted laser desorption ionization (MALDI) integrated mass spectrometry imaging (MSI) was proposed to investigate tissue-specific metabolic alterations in the kidneys of high-fat diet-fed and streptozotocin (STZ)-treated DN rats and the therapeutic effect of astragaloside IV, a potential anti-diabetic drug, against DN. As a result, a wide range of functional metabolites including sugars, amino acids, nucleotides and their derivatives, fatty acids, phospholipids, sphingolipids, glycerides, carnitine and its derivatives, vitamins, peptides, and metal ions associated with DN were identified and their unique distribution patterns in the rat kidney were visualized with high chemical specificity and high spatial resolution. These region-specific metabolic disturbances were ameliorated by repeated oral administration of astragaloside IV (100 mg/kg) for 12 weeks. This study provided more comprehensive and detailed information about the tissue-specific metabolic reprogramming and molecular pathological signature in the kidney of diabetic rats. These findings highlighted the promising potential of AFADESI and MALDI integrated MSI based metabolomics approach for application in metabolic kidney diseases.
深入了解糖尿病肾病（DN）中组织特异性代谢重编程对于更准确地理解分子病理特征和开发新的治疗策略至关重要。在本研究中，提出了一种基于气流辅助解吸电喷雾电离（AFADESI）和基质辅助激光解吸电离（MALDI）集成质谱成像（MSI）的空间分辨代谢组学方法，以研究高脂饮食喂养和链脲佐菌素（STZ）处理的DN大鼠肾脏中的组织特异性代谢改变，以及潜在抗糖尿病药物黄芪甲苷IV对DN的治疗效果。结果，鉴定出了包括糖类、氨基酸、核苷酸及其衍生物、脂肪酸、磷脂、鞘脂、甘油酯、肉碱及其衍生物、维生素、肽和与DN相关的金属离子等多种功能性代谢物，并以高化学特异性和高空间分辨率可视化了它们在大鼠肾脏中的独特分布模式。通过重复口服黄芪甲苷IV（100 mg/kg）12周，这些区域特异性代谢紊乱得到改善。本研究提供了关于糖尿病大鼠肾脏中组织特异性代谢重编程和分子病理特征更全面、详细的信息。这些发现突出了基于AFADESI和MALDI集成MSI的代谢组学方法在代谢性肾脏疾病应用中的广阔前景。
