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代谢组学方法在男性下尿路症状中的应用:寻找可能的生物标志物和新治疗方法的潜在靶点。

Metabolomics Approach to Male Lower Urinary Tract Symptoms: Identification of Possible Biomarkers and Potential Targets for New Treatments.

机构信息

Departments of Urology and Health Sciences (HY), Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan.

Departments of Urology and Health Sciences (HY), Graduate School of Medical Sciences, University of Yamanashi, Yamanashi, Japan.

出版信息

J Urol. 2018 May;199(5):1312-1318. doi: 10.1016/j.juro.2017.11.070. Epub 2017 Nov 22.

DOI:10.1016/j.juro.2017.11.070
PMID:29175111
Abstract

PURPOSE

We identified metabolites using a metabolomics approach and investigated the association between these metabolites and lower urinary tract symptoms.

MATERIALS AND METHODS

We used a 24-hour bladder diary and I-PSS (International Prostate Symptom Score) to assess micturition behavior and lower urinary tract symptoms in 58 male patients without apparent neurological disease. Lower urinary tract symptoms were defined as a total I-PSS score of 8 or greater. Patients with a score of 7 or less were placed in the control group. A comprehensive study of plasma metabolites was also performed by capillary electrophoresis time-of-flight mass spectrometry. Metabolites were compared between the lower urinary tract symptoms and control groups using the Mann-Whitney U test. Biomarkers of male lower urinary tract symptoms from the metabolites were analyzed using multivariable logistic regression analysis to determine the OR.

RESULTS

Of the 58 men 32 were in the lower urinary tract symptoms group and the remaining 26 were in the control group. The 24-hour bladder diary showed that nocturnal urine volume, 24-hour micturition frequency, nocturnal micturition frequency and the nocturia index were significantly higher in the lower urinary tract symptoms group. Metabolomics analysis identified 60 metabolites from patient plasma. Multivariate analysis revealed that increased glutamate and decreased arginine, asparagine and inosine monophosphate were significantly associated with lower urinary tract symptoms in males. Decreases in citrulline and glutamine could also be associated with male lower urinary tract symptoms.

CONCLUSIONS

Male lower urinary tract symptoms may develop due to abnormal metabolic processes in some pathways. Potential new treatments for lower urinary tract symptoms can be developed by identifying changes in the amino acid profiles.

摘要

目的

我们采用代谢组学方法鉴定代谢物,并探讨这些代谢物与下尿路症状之间的关联。

材料与方法

我们使用 24 小时膀胱日记和 I-PSS(国际前列腺症状评分)评估 58 名无明显神经疾病的男性患者的排尿行为和下尿路症状。下尿路症状定义为 I-PSS 总分≥8 分。总分 7 分或以下的患者被归入对照组。我们还通过毛细管电泳飞行时间质谱对血浆代谢物进行了全面研究。使用 Mann-Whitney U 检验比较下尿路症状组和对照组之间的代谢物。使用多变量逻辑回归分析对来自代谢物的男性下尿路症状的生物标志物进行分析,以确定 OR。

结果

58 名男性中,32 名处于下尿路症状组,其余 26 名处于对照组。24 小时膀胱日记显示,下尿路症状组的夜间尿量、24 小时排尿次数、夜间排尿次数和夜尿指数明显较高。代谢组学分析从患者血浆中鉴定出 60 种代谢物。多变量分析显示,谷氨酸增加和精氨酸、天冬酰胺和肌苷单磷酸减少与男性下尿路症状显著相关。瓜氨酸和谷氨酰胺的减少也可能与男性下尿路症状有关。

结论

男性下尿路症状可能是由于某些途径的代谢过程异常而发生的。通过鉴定氨基酸谱的变化,可以开发出治疗下尿路症状的新方法。

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