目的:从代谢的角度,通过非靶向代谢组学探究IgA肾病(immunoglobulin anephropathy, IgAN)患者血清代谢紊乱的模式,并分析参与IgAN发生、发展的重要代谢物。方法:对包头医学院第一附属医院15例IgAN患者和15例健康对照者的血清样品进行非靶向代谢组学分析,筛选出差异代谢物并进行通路分析,以揭示IgAN的重要代谢通路。同时,探讨IgAN代谢产物之间以及代谢产物与临床病理特征之间的相关性,阐明代谢物在IgAN中的意义。结果:(1)IgAN患者血清代谢物与健康对照组相比存在显著性差异,发现了包括氨基酸、尿毒症毒素、脂肪酸在内的20种关键性代谢物以及色氨酸代谢、苯丙氨酸和酪氨酸代谢、柠檬酸循环、酮体代谢、肉碱合成途径5条差异性代谢途径,有助于进一步了解IgAN的代谢网络;(2)与IgAN显著相关的代谢途径是芳香族氨基酸(即苯丙氨酸、酪氨酸和色氨酸)代谢;(3)差异代谢物与IgAN患者的临床指标有显著的相关性,代谢物的变化与节段肾小球硬化、肾小球系膜细胞增多有关。结论:IgAN患者血清代谢物的变化参与了IgAN发生、发展。
Objective: To explore the pattern of serum metabolic disorders in patients with immunoglobulin anephropathy (IgAN) from the perspective of metabolism through non-targeted metabolomics, and to analyze the important metabolites involved in the occurrence and development of IgAN. Methods: Non-targeted metabolomics analysis was conducted on serum samples from 15 patients with IgAN and 15 healthy controls from the First Affiliated Hospital of Baotou Medical College to screen for differential metabolites. Pathway analysis was also performed to reveal the critical metabolic pathways in IgAN. Additionally, the correlations between IgAN metabolites, as well as between metabolites and clinicopathological features were explored to clarify the significance of metabolites in IgAN. Results: (1) There were significant differences in serum metabolites between IgAN patients and healthy controls. Twenty key metabolites including amino acids, uremic toxins and fatty acids, as well as five differential metabolic pathways including tryptophan metabolism, phenylalanine and tyrosine metabolism, citric acid cycle, ketone body metabolism and carnitine synthesis pathway were found, which were helpful to further understand the metabolic network of IgAN. (2)The metabolic pathway significantly associated with IgAN was the metabolism of aromatic amino acids (ie, phenylalanine, tyrosine and tryptophan). (3) There was a significant correlation between differential metabolites and clinical indicators of IgAN patients. The changes of metabolites were related to segmental glomerulosclerosis and increased mesangial cells. Conclusion: The changes of serum metabolites in IgAN patients are involved in the occurrence and development of IgAN.
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