Hu Changfeng, Du Yu, Xu Xiaofen, Li Haichang, Duan Qiao, Xie Zhijun, Wen Chengping, Han Xianlin
College of Basic Medical Sciences, Zhejiang Chinese Medical University, 548 Bingwen Road, Hangzhou 310053, China.
First Clinical Medical College, Zhejiang Chinese Medical University, 548 Bingwen Road, Hangzhou 310053, China.
Metabolites. 2021 Feb 27;11(3):142. doi: 10.3390/metabo11030142.
Lupus nephritis (LN) is an inflammatory renal disease of patients with systemic lupus erythematosus with lots of immune complexes deposited in kidneys. Accumulated studies have demonstrated the close relationships among dyslipidaemia, inflammation, and autoimmune response, and oxidative stress in the patients. Lipids play numerous important roles in biological process and cellular functions. Herein, shotgun lipidomics was employed to quantitatively analyze cellular lipidomes in the renal tissue of MRL/lpr mice in the progression of LN (including pre-LN and LN state) with/without treated with glucocorticoids (GCs). The levels of cytokines (i.e., TNF-α (Tumor necrosis factor alpha) and IL-6 (Interleukin 6)) in the serum were measured by ELISA (enzyme-linked immunosorbent assay) kits. Renal histopathological changes and C3 deposition in the glomeruli of the mice were also determined. Lipidomics analysis revealed that the ectopic fat deposition and the aberrant metabolism of lipids that were relevant to oxidative stress (e.g., 4-hydroxyalkenal, ceramide, lysophospholipid species, etc.) always existed in the development of LN. Moreover, the anti-inflammatory FAHFA (fatty acid ester of hydroxyl fatty acid) species in the kidney tissue could largely reflect the severity of LN. Thus, they were a potential early biomarker for LN. In addition, the study also revealed that treatment with GCs could prevent the progression of LN, but greatly aggravate the aberrant metabolism of the lipids, particularly when used for a long time.
狼疮性肾炎（LN）是系统性红斑狼疮患者的一种炎症性肾脏疾病，有大量免疫复合物沉积于肾脏。越来越多的研究表明，血脂异常、炎症、自身免疫反应以及患者体内的氧化应激之间存在密切关系。脂质在生物过程和细胞功能中发挥着众多重要作用。在此，我们采用鸟枪法脂质组学技术，对MRL/lpr小鼠在狼疮性肾炎进展过程中（包括狼疮性肾炎前期和狼疮性肾炎状态），无论是否接受糖皮质激素（GCs）治疗的肾脏组织中的细胞脂质组进行定量分析。通过酶联免疫吸附测定（ELISA）试剂盒检测血清中细胞因子（即肿瘤坏死因子α（TNF-α）和白细胞介素6（IL-6））的水平。还测定了小鼠肾小球的肾脏组织病理学变化和C3沉积情况。脂质组学分析表明，在狼疮性肾炎的发展过程中，始终存在与氧化应激相关的异位脂肪沉积和脂质代谢异常（如4-羟基烯醛、神经酰胺、溶血磷脂种类等）。此外，肾脏组织中的抗炎性羟基脂肪酸脂肪酸酯（FAHFA）种类在很大程度上可以反映狼疮性肾炎的严重程度。因此，它们是狼疮性肾炎潜在的早期生物标志物。此外，该研究还表明，糖皮质激素治疗可以预防狼疮性肾炎的进展，但会极大地加重脂质代谢异常，尤其是长期使用时。
