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氨基酸平衡失调作为糖尿病视网膜病变诊断和预后的潜在血清代谢物生物标志物:一项代谢组学研究

Dysregulation of amino acids balance as potential serum-metabolite biomarkers for diagnosis and prognosis of diabetic retinopathy: a metabolomics study.

作者信息

Amiri-Dashatan Nasrin, Etemadi Samira Motedayen, Besharati Shahin, Farahani Masoumeh, Moghaddam Arezoo Karimi

机构信息

Zanjan Metabolic Diseases Research Center, Zanjan University of Medical Sciences, Zanjan, Iran.

Proteomics Research Center, Shahid Beheshti University of Medical Sciences, Tehran, Iran.

出版信息

J Diabetes Metab Disord. 2024 Jul 20;23(2):2031-2042. doi: 10.1007/s40200-024-01462-y. eCollection 2024 Dec.

Abstract

OBJECTIVES

Diabetic retinopathy (DR), an earnest complication of diabetes, is one of the most common causes of blindness worldwide. This study aimed to investigate the altered metabolites in the serum of non-DR (NDR) and DR including non-proliferative diabetic retinopathy (NPDR), and proliferative diabetic retinopathy (PDR) subjects.

METHODS

In this study, the 1HNMR platform was applied to reveal the discriminating serum metabolites in three diabetic groups based on the status of their complications: T2D or NDR ( = 15), NPDR, ( = 15), and PDR ( = 15) groups. Multivariate analyses include principal component analysis (PCA) and Partial Least Structures-Discriminant Analysis (PLS-DA) analysis that were performed using R software. The main metabolic pathways were also revealed by KEGG pathway enrichment analysis.

RESULTS

The results revealed the significantly different metabolites include 10 metabolites of the NPDR versus PDR group, 24 metabolites of the PDR versus NDR group, and 25 metabolites of the NPDR versus NDR group. The results showed that the significantly altered metabolites in DR compared with NDR serum samples mainly belonged to amino acids. The most important pathways between NPDR/PDR, and NDR/DR groups include ascorbate and aldarate metabolism, galactose metabolism, glutathione metabolism, and tryptophan metabolism, respectively. In addition, some metabolites were detected for the first time.

CONCLUSIONS

We created a metabolomics profile for NDR, PDR and NPDR groups. The impairment in the ascorbate/aldarate, galactose, and especially amino acids metabolism was identified as metabolic dysregulation associated with DR, which may provide new insights into potential pathogenesis pathways for DR.

摘要

目的

糖尿病视网膜病变(DR)是糖尿病的一种严重并发症,是全球范围内最常见的致盲原因之一。本研究旨在调查非糖尿病视网膜病变(NDR)以及糖尿病视网膜病变(包括非增殖性糖尿病视网膜病变(NPDR)和增殖性糖尿病视网膜病变(PDR))患者血清中代谢物的变化。

方法

在本研究中,基于并发症状况,应用1HNMR平台揭示三个糖尿病组(T2D或NDR(n = 15)、NPDR(n = 15)和PDR(n = 15)组)中具有鉴别意义的血清代谢物。多变量分析包括使用R软件进行的主成分分析(PCA)和偏最小二乘判别分析(PLS-DA)。通过KEGG通路富集分析也揭示了主要的代谢途径。

结果

结果显示,NPDR与PDR组之间有10种代谢物、PDR与NDR组之间有24种代谢物、NPDR与NDR组之间有25种代谢物存在显著差异。结果表明,与NDR血清样本相比,DR中显著改变的代谢物主要属于氨基酸。NPDR/PDR与NDR/DR组之间最重要的途径分别包括抗坏血酸和醛糖代谢、半乳糖代谢、谷胱甘肽代谢和色氨酸代谢。此外,还首次检测到一些代谢物。

结论

我们创建了NDR、PDR和NPDR组的代谢组学图谱。抗坏血酸/醛糖、半乳糖,尤其是氨基酸代谢的损伤被确定为与DR相关的代谢失调,这可能为DR的潜在发病机制途径提供新的见解。

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