Zhang Xin, Liu Yanhua, Yang Shu, Gao Xin, Wang Shuo, Wang Zhaoying, Zhang Chen, Zhou Zhi, Chen Yanhua, Wang Zhonghua, Abliz Zeper
Key Laboratory of Mass Spectrometry Imaging and Metabolomics, Minzu University of China, National Ethnic Affairs Commission, Beijing 100081, China.
Center for Imaging and Systems Biology, College of Life and Environmental Sciences, Minzu University of China, 27 Zhongguancun South Avenue, Beijing 100081, China.
Metabolites. 2023 Feb 22;13(3):324. doi: 10.3390/metabo13030324.
Understanding the renal region-specific metabolic alteration in different animal models of diabetic nephropathy (DN) is critical for uncovering the underlying mechanisms and for developing effective treatments. In the present study, spatially resolved metabolomics based on air flow-assisted desorption electrospray ionization mass spectrometry imaging (AFADESI-MSI) was used to compare the local metabolic changes in the kidneys of HFD/STZ-induced diabetic rats and db/db mice. As a result, a total of 67 and 59 discriminating metabolites were identified and visualized in the kidneys of the HFD/STZ-induced diabetic rats and db/db mice, respectively. The result showed that there were significant region-specific changes in the glycolysis, TCA cycle, lipid metabolism, carnitine metabolism, choline metabolism, and purine metabolism in both DN models. However, the regional levels of the ten metabolites, including glucose, AMP, eicosenoic acid, eicosapentaenoic acid, Phosphatidylserine (36:1), Phosphatidylserine (36:4), Phosphatidylethanolamine (34:1), Phosphatidylethanolamine (36:4), Phosphatidylcholine (34:2), Phosphatidylinositol (38:5) were changed in reversed directions, indicating significant differences in the local metabolic phenotypes of these two commonly used DN animal models. This study provides comprehensive and in-depth analysis of the differences in the tissue and molecular pathological features in diabetic kidney injury in HFD/STZ-induced diabetic rats and db/db mice.
了解糖尿病肾病（DN）不同动物模型中肾脏区域特异性代谢改变对于揭示潜在机制和开发有效治疗方法至关重要。在本研究中，基于气流辅助解吸电喷雾电离质谱成像（AFADESI-MSI）的空间分辨代谢组学被用于比较高脂饮食/链脲佐菌素（HFD/STZ）诱导的糖尿病大鼠和db/db小鼠肾脏中的局部代谢变化。结果，在HFD/STZ诱导的糖尿病大鼠和db/db小鼠的肾脏中分别鉴定并可视化了总共67种和59种有鉴别意义的代谢物。结果表明，在两种DN模型中，糖酵解、三羧酸循环、脂质代谢、肉碱代谢、胆碱代谢和嘌呤代谢均存在显著的区域特异性变化。然而，包括葡萄糖、AMP、二十碳烯酸、二十碳五烯酸、磷脂酰丝氨酸（36:1）、磷脂酰丝氨酸（36:4）、磷脂酰乙醇胺（34:1）、磷脂酰乙醇胺（36:4）、磷脂酰胆碱（34:2）、磷脂酰肌醇（38:5）在内的十种代谢物的区域水平呈相反方向变化，表明这两种常用的DN动物模型在局部代谢表型上存在显著差异。本研究对HFD/STZ诱导的糖尿病大鼠和db/db小鼠糖尿病肾损伤的组织和分子病理特征差异进行了全面深入的分析。
