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Spatial-resolved metabolomics reveals tissue-specific metabolic reprogramming in diabetic nephropathy by using mass spectrometry imaging

查看全文 作　　者：Zhonghua [1,2,5]Wang;Wenqing [1,2]Fu;Meiling [1,2]Huo;Bingshu [2]He;Yaqi [2]Liu;Lu [3]Tian;Wanfang [3]Li;Zhi [1,2]Zhou;Baili [4]Wang;Jianzhen [4]Xia;Yanhua [1,2]Chen;Jinfeng [3]Wei;Zeper [1,2,5]Abliz 高影响力作者 机构地区：[1]Key Laboratory of Mass Spectrometry Imaging and Metabolomics(Minzu University of China),National Ethnic Affairs Commission,Beijing 100081,China;[2]College of Life and Environmental Sciences,Minzu University of China,Beijing 100081,China;[3]New Drug Safety Evaluation Center,Institute of Materia Medica,Peking Union Medical College,Beijing 100050,China;[4]School Hospital,Minzu University of China,Beijing 100081,China;[5]Key Laboratory of Ethnomedicine of Ministry of Education,School of Pharmacy,Minzu University of China,Beijing 100081,China高影响力机构 出　　处：《Acta Pharmaceutica Sinica B》索引2021年第11卷第11期,共13页高影响力期刊 基　　金：supported by the National Natural Science Foundation of China(No.81803483,No.21927808);National Key Research and Development Program of China(No.2017YFC1704006)。 摘　　要：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 flowassisted 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 astragalosideⅣ,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. 关 键 词：Spatial-resolved metabolomics Mass spectrometry imaging Diabetic nephropathy Metabolic reprogramming AstragalosideⅣ
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