血浆氧脂分析揭示糖尿病肾病中ARA/5-HETE代谢的逐步激活。

IF 4.1 2区 医学 Q1 BIOCHEMISTRY & MOLECULAR BIOLOGY
Chunyu Zhou, Xianhui Liang, Jiao Wang, Jia Guo, Qing Zhang, Pei Wang
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引用次数: 0

摘要

糖尿病肾病(DKD)是糖尿病伴氧脂代谢紊乱的一种非常普遍的并发症。我们的研究表征了与DKD逐步进展相关的血浆氧脂素。采用超高效液相色谱-串联质谱法(UPLC-MS/MS)对DKD或T2DM患者和健康人群血浆样品中的141种氧脂类进行定量分析,检测组(每组n=40)和验证组(每组n=20)。采用正交偏最小二乘判别分析(OPLS-DA)和受试者工作特征(ROC)曲线对与DKD相关的关键氧脂类进行鉴定。采用多项式回归、Pearson相关和logistic回归分析,评估其与反映DKD进展的临床指标的相关性以及诊断能力。我们的氧化脂谱分析显示,在测试队列中有55种显著变化,在验证队列中有42种显著变化。检测队列中的ARA、5-HETE、5-oxoETE、12-HETE和13(S)-HpODE,验证队列中的ARA、5-HETE、5-oxoETE、20- hydroxygf2 α和8,9- eet被筛选为区分DKD组的关键氧脂类。血浆中ARA、5-HETE和5-oxoETE水平的升高与肾小球滤过率(eGFR)密切相关。结合血浆ARA、5-HETE和5-oxoETE水平的诊断模型对DKD有较好的诊断效果。总的来说,我们的研究揭示了氧化脂素代谢谱,暗示ARA/5-HETE代谢的激活与DKD的逐步进展有关,这为DKD的早期识别和治疗策略提供了基础。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Plasma oxylipin profiling reveals the step-wise activation of ARA/5-HETE metabolism in diabetic kidney disease.

Diabetic kidney disease (DKD) is a highly prevalent complication of diabetes concomitant with disordered oxylipin metabolism. Our study characterize the plasma oxylipins associated with the step-wise progression of DKD. An ultra-performance liquid chromatography tandem mass spectrometry (UPLC-MS/MS) method was performed to quantify 141 kinds of oxylipins in plasma samples of patients with DKD or T2DM and healthy individuals, both in the test cohort (n=40 for each group) and the validation cohort (n=20 for each group). The key oxylipins associated with DKD were identified by orthogonal partial least-squares discriminant analysis (OPLS-DA) and receiver-operating characteristic (ROC) curve. Polynomial regression, Pearson's correlation and logistic regression analyses were performed to assess their correlation with the clinical indicators reflecting DKD progression, as well as their diagnostic abilities. Our oxylipin profiling presented the significant alterations of 55 kinds in the test cohort and 42 kinds in the validation cohort. ARA, 5-HETE, 5-oxoETE, 12-HETE and 13(S)-HpODE in the test cohort, as well as ARA, 5-HETE, 5-oxoETE, 20-hydroxyPGF2α and 8,9-EET in the validation cohort were screened as the key oxylipins distinguishing DKD group. The increased plasma levels of ARA, 5-HETE and 5-oxoETE were strongly correlated with estimated glomerular filtration rate (eGFR). The diagnostic model combining the plasma levels of ARA, 5-HETE and 5-oxoETE indicated an excellent diagnostic performance for DKD. Collectively, our study disclosed the profiling of oxylipin metabolism, implicating the activation of ARA/5-HETE metabolism associated with the step-wise progression of DKD, which provide the basis for early identification and therapeutic strategies for DKD.

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来源期刊
Journal of Lipid Research
Journal of Lipid Research 生物-生化与分子生物学
CiteScore
11.10
自引率
4.60%
发文量
146
审稿时长
41 days
期刊介绍: The Journal of Lipid Research (JLR) publishes original articles and reviews in the broadly defined area of biological lipids. We encourage the submission of manuscripts relating to lipids, including those addressing problems in biochemistry, molecular biology, structural biology, cell biology, genetics, molecular medicine, clinical medicine and metabolism. Major criteria for acceptance of articles are new insights into mechanisms of lipid function and metabolism and/or genes regulating lipid metabolism along with sound primary experimental data. Interpretation of the data is the authors’ responsibility, and speculation should be labeled as such. Manuscripts that provide new ways of purifying, identifying and quantifying lipids are invited for the Methods section of the Journal. JLR encourages contributions from investigators in all countries, but articles must be submitted in clear and concise English.
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