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血浆和尿液中花生四烯酸衍生的类二十烷酸浓度与糖尿病肾病相关。

Plasma and urinary concentrations of arachidonic acid-derived eicosanoids are associated with diabetic kidney disease.

作者信息

Mota-Zamorano Sonia, Robles Nicolás R, Lopez-Gomez Juan, Cancho Bárbara, González Luz M, Garcia-Pino Guadalupe, Navarro-Pérez María Luisa, Gervasini Guillermo

机构信息

Department of Medical and Surgical Therapeutics, Division of Pharmacology, Medical School, University of Extremadura, Badajoz, Spain.

Service of Nephrology, Badajoz University Hospital, Badajoz, Spain.

出版信息

EXCLI J. 2021 Mar 18;20:698-708. doi: 10.17179/excli2021-3408. eCollection 2021.

DOI:10.17179/excli2021-3408
PMID:34040498
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC8144539/
Abstract

Preclinical studies indicate that arachidonic acid (AA)-derived eicosanoids contribute to hyperglycemia-induced kidney injury. We aimed to determine whether plasma and/or urinary levels of dihydroxyeicosatrienoic (DHETs) and 20-hydroxyeicosatetraenoic (20-HETE) acids are associated with diabetic kidney disease (DKD). A total of 334 subjects (132 DKD patients and 202 non-diabetic individuals) were studied. Plasma levels of 11,12-DHET, 14,15-DHET and 20-HETE were measured by LC/MS/MS. Urinary 20-HETE concentrations were determined by immunoenzymatic assay. Subjects with normoalbuminuria had larger 20-HETE-to-creatinine urinary ratios (20-HETE/Cr) than those with micro and macroalbuminuria (p=0.012). Likewise, participants with eGFR>60 ml/min/1.73 m had higher plasma levels of 14,15-DHET (p=0.039) and 20-HETE/Cr ratios (p=0.007). Concentrations of 14,15-DHET, 11,12-DHET and 20-HETE/Cr were significantly lower in DKD patients. Median values for non-diabetic vs. DKD were, respectively, 493 (351.0-691.5) vs. 358 (260.5-522) ng/L, p=3e-5; 262 (183.5-356.0) vs. 202 (141.5-278.0) ng/L, p=1e-4 and 5.26 (1.68-11.65) vs. 2.53 (1.01-6.28) ng/mgCr, p=0.010. In addition, 20-HETE/Cr ratios were higher in patients with non-proteinuric DKD than in those with typical DKD (p=0.020). When only individuals with impaired filtration were considered, 14,15-DHET and 11,12-DHET levels were still higher in non-diabetic subjects (p=0.002 and p=0.006, respectively). Our results indicate that AA-derived eicosanoids may play a relevant role in DKD.

摘要

临床前研究表明，花生四烯酸（AA）衍生的类二十烷酸会导致高血糖诱导的肾损伤。我们旨在确定二羟基二十碳三烯酸（DHETs）和20-羟基二十碳四烯酸（20-HETE）的血浆和/或尿液水平是否与糖尿病肾病（DKD）相关。共研究了334名受试者（132例DKD患者和202名非糖尿病个体）。通过液相色谱/串联质谱法测量11,12-DHET、14,15-DHET和20-HETE的血浆水平。通过免疫酶测定法测定尿液中20-HETE的浓度。正常白蛋白尿受试者的尿20-HETE与肌酐比值（20-HETE/Cr）高于微量和大量白蛋白尿受试者（p=0.012）。同样，估算肾小球滤过率（eGFR）>60 ml/min/1.73 m²的参与者血浆中14,15-DHET水平更高（p=0.039），20-HETE/Cr比值也更高（p=0.007）。DKD患者中14,15-DHET、11,12-DHET浓度和20-HETE/Cr显著降低。非糖尿病与DKD患者的中位数分别为493（351.0 - 691.5）ng/L vs. 358（260.5 - 522）ng/L，p = 3×10⁻⁵；2,62（183.5 - 356.0）ng/L vs. 202（141.5 - 278.0）ng/L，p = 1×10⁻⁴；以及5.26（1.68 - 11.65）vs. 2.53（1.01 - 6.28）ng/mgCr，p = （此处可能有误，原文为p=0.010，推测应为p = 0.010）。此外，非蛋白尿性DKD患者的20-HETE/Cr比值高于典型DKD患者（p=0.020）。当仅考虑滤过功能受损的个体时，非糖尿病受试者的14,15-DHET和11,12-DHET水平仍然更高（分别为p=0.002和p=0.006）。我们的结果表明，AA衍生的类二十烷酸可能在DKD中起相关作用。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfee/8144539/efd9e981f4ce/EXCLI-20-698-g-006.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfee/8144539/476baf1a8ca8/EXCLI-20-698-t-001.jpg
https://cdn.ncbi.nlm.nih.gov/pmc/blobs/dfee/8144539/e049478492b4/EXCLI-20-698-g-001.jpg
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