关键词： ADP, adenosine diphosphate AFADESI, air flow-assisted desorption electrospray ionization AGEs, advanced glycation end products AMP, adenosine monophosphate AMPK, adenosine monophosphate activated protein kinase AST, astragaloside IV ATP, adenosine triphosphate Astragaloside IV BUN, blood urea nitrogen CL, cardiolipin Cre, creatinine DAG, diacylglycerol DESI, desorption electrospray ionization DM, diabetes mellitus DN, diabetic nephropathy DPA, docosapentaenoic acid Diabetic nephropathy ESKD, end-stage kidney disease FBG, fasting blood glucose GLU, glucose GMP, guanosine monophosphate GSH, glutathione H&E, hematoxylin and eosin HPLC, high-performance liquid chromatography HbA1c, glycosylated hemoglobin LysoPC, lysophosphatidylcholine LysoPG, lysophosphatidylglycerol MALDI, matrix-assisted laser desorption ionization MS, mass spectrometry MSI, mass spectrometry imaging Mass spectrometry imaging Metabolic reprogramming NMR, nuclear magnetic resonance Na-CMC, sodium carboxymethyl cellulose PA, phosphatidic acid PC, phosphatidylcholine PE, phosphatidylethanolamine PG, phosphatidylglycerol PPP, pentose phosphate pathway PS, phosphatidylserine PUFA, polyunsaturated fatty acids ROI, regions of interest ROS, reactive oxygen species SDH, succinate dehydrogenase SGLTs, sodium-glucose cotransporters SM, sphingomyelin STZ, streptozotocin Spatial-resolved metabolomics TCA, tricarboxylic acid TCHO, total cholesterol TG, triglyceride UMP, uridine monophosphate VIP, variable importance in projection p-AMPK, phosphorylated adenosine monophosphate activated protein kinase ADP, adenosine diphosphate AFADESI, air flow-assisted desorption electrospray ionization AGEs, advanced glycation end products AMP, adenosine monophosphate AMPK, adenosine monophosphate activated protein kinase AST, astragaloside IV ATP, adenosine triphosphate Astragaloside IV BUN, blood urea nitrogen CL, cardiolipin Cre, creatinine DAG, diacylglycerol DESI, desorption electrospray ionization DM, diabetes mellitus DN, diabetic nephropathy DPA, docosapentaenoic acid Diabetic nephropathy ESKD, end-stage kidney disease FBG, fasting blood glucose GLU, glucose GMP, guanosine monophosphate GSH, glutathione H&E, hematoxylin and eosin HPLC, high-performance liquid chromatography HbA1c, glycosylated hemoglobin LysoPC, lysophosphatidylcholine LysoPG, lysophosphatidylglycerol MALDI, matrix-assisted laser desorption ionization MS, mass spectrometry MSI, mass spectrometry imaging Mass spectrometry imaging Metabolic reprogramming NMR, nuclear magnetic resonance Na-CMC, sodium carboxymethyl cellulose PA, phosphatidic acid PC, phosphatidylcholine PE, phosphatidylethanolamine PG, phosphatidylglycerol PPP, pentose phosphate pathway PS, phosphatidylserine PUFA, polyunsaturated fatty acids ROI, regions of interest ROS, reactive oxygen species SDH, succinate dehydrogenase SGLTs, sodium-glucose cotransporters SM, sphingomyelin STZ, streptozotocin Spatial-resolved metabolomics TCA, tricarboxylic acid TCHO, total cholesterol TG, triglyceride UMP, uridine monophosphate VIP, variable importance in projection p-AMPK, phosphorylated adenosine monophosphate activated protein kinase

来  源：   DOI：10.1016/j.apsb.2021.05.013   PDF(Sci-hub)   PDF(Pubmed)

Abstract：
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.
摘要：
关于糖尿病肾病（DN）中组织特异性代谢重编程的详细知识对于更准确地理解分子病理学特征和开发新的治疗策略至关重要。在本研究中,提出了一种基于空气流动辅助解吸电喷雾电离（AFADESI）和基质辅助激光解吸电离（MALDI）整合质谱成像（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）治疗的DN大鼠肾脏的组织特异性代谢变化以及黄芪甲苷的治疗作用，一种潜在的抗糖尿病药物，对DN。因此,广泛的功能性代谢物，包括糖，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，并鉴定了与DN相关的金属离子，并以高化学特异性和高空间分辨率显示了它们在大鼠肾脏中的独特分布模式。通过反复口服黄芪甲苷（100mg/kg）12周可改善这些特定区域的代谢紊乱。这项研究提供了有关糖尿病大鼠肾脏组织特异性代谢重编程和分子病理学特征的更全面和详细信息。这些发现强调了AFADESI和MALDI整合的基于MSI的代谢组学方法在代谢性肾脏疾病中的应用潜力。
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