Department of Nephrology, Affiliated Bao'an Hospital of Shenzhen, The Second School of Clinical Medicine, Southern Medical University, Shenzhen, Guangdong 518000, P.R. China.
Int J Mol Med. 2019 Jul;44(1):172-184. doi: 10.3892/ijmm.2019.4176. Epub 2019 Apr 30.
To determine the differences in plasma metabolism between healthy patients and patients with hyperuricaemia and gouty nephropathy, the present study identified differentially expressed metabolites associated with gouty nephropathy. Furthermore, the NLRP3 inflammasome signalling pathway in gouty nephropathy was explored, and the mechanism of hyperuricaemia‑induced renal damage. Adult male patients examined between July 2016 and June 2017 were selected as the patient cohort for the present study from the Affiliated Bao'an Hospital of Shenzhen, Southern Medical University (Shenzhen, China). These patients were divided into three groups of 30 patients each: Control, hyperuricaemia and gouty nephropathy groups. The expression levels of NLRP3, ASC and caspase‑1 mRNA and protein were detected in peripheral blood mononuclear cells, and the plasma levels of IL‑1β and IL‑18. Ultra‑performance liquid chromatography coupled with quadrupole time‑of‑flight mass spectrometry was used to determine differential levels of metabolites between patients from different groups, in order to identify potential biomarkers. The expression of the NLRP3 inflammasome in peripheral blood mononuclear cells, and the levels of IL‑1β and IL‑18 in the plasma were increased in the gouty nephropathy group compared with the control and hyperuricaemia groups. In addition, 46 metabolites were identified as potential plasma metabolic biomarkers that were able to distinguish gouty nephropathy from hyperuricaemia. The majority of these metabolites were involved in lipid metabolism, in particular the activity of phospholipase Α2 and β‑oxidation. These data indicated that lipid metabolism and the NLRP3 inflammasome serve a pivotal role in gouty nephropathy. In addition, the results suggested that lipids may mediate the progression of gouty nephropathy through the activity of phospholipase A2, β‑oxidation and activation of the NLRP3 inflammasome.
为了确定健康患者与高尿酸血症和痛风性肾病患者之间血浆代谢的差异,本研究鉴定了与痛风性肾病相关的差异表达代谢物。此外,还探讨了痛风性肾病中 NLRP3 炎性体信号通路,以及高尿酸血症引起的肾损伤的机制。本研究选取 2016 年 7 月至 2017 年 6 月期间在南方医科大学附属深圳宝安医院(中国深圳)检查的成年男性患者作为患者队列,将这些患者分为三组,每组 30 例:对照组、高尿酸血症组和痛风性肾病组。检测外周血单个核细胞中 NLRP3、ASC 和 caspase-1mRNA 和蛋白的表达水平,检测血浆中 IL-1β 和 IL-18 的水平。采用超高效液相色谱-四极杆飞行时间质谱联用技术测定不同组别患者之间的代谢物差异水平,以鉴定潜在的生物标志物。与对照组和高尿酸血症组相比,痛风性肾病组外周血单个核细胞中 NLRP3 炎性体的表达以及血浆中 IL-1β 和 IL-18 的水平均升高。此外,鉴定出 46 种潜在的血浆代谢生物标志物,可将痛风性肾病与高尿酸血症区分开来。这些代谢物大多数与脂质代谢有关,特别是磷脂酶 A2 和β-氧化的活性。这些数据表明,脂质代谢和 NLRP3 炎性体在痛风性肾病中起关键作用。此外,结果表明,脂质可能通过磷脂酶 A2、β-氧化和 NLRP3 炎性体的激活来介导痛风性肾病的进展。