Wang Yihan, Ren Yating, Hong Tao, Lu Dingqi, Zhang Fan, Cao Yi, Wang Xinchang
Second Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
First Clinical Medical College, Zhejiang Chinese Medical University, Hangzhou, People's Republic of China.
J Inflamm Res. 2022 Dec 5;15:6569-6580. doi: 10.2147/JIR.S391595. eCollection 2022.
Neuropsychiatric lupus (NPSLE) is one of the important manifestations of systemic lupus erythematosus. Previous studies mainly focused on the disruption of the blood-brain barrier and the production of brain-reactive autoantibodies, However, there is no comprehensive lipidomic analysis in NPSLE. Therefore, this research evaluated the lipidomic analysis in the hippocampus and liver of NPSLE mice with mood disorders, to explore the influence of the liver-brain axis on this disease.
MRL/lpr mice and MRL/mpj mice were respectively used as NPSLE and control groups. Behavioral tests and systemic disease characteristics of mice were assessed at the age of 18 weeks. Ultra-Performance Liquid Chromatography-Tandem Mass Spectrometry (UPLC-MS/MS) was used for lipid metabolite determination. Multivariate statistical analysis was used to identify lipid metabolites that were differentially expressed in two groups.
Our results showed that 355 and 405 lipid metabolites were differentially expressed between the NPSLE and control groups in the hippocampus and liver. According to the pathway enrichment analysis, several pathways were affected, and the glycerophospholipid metabolism pathway was most relevant to the mouse's depressive behavior.
Based on UPLC-MS/MS, the results provide evidence for how the liver-brain axis affects NPSLE and improve the understanding of NPSLE pathogenesis.
神经精神性狼疮(NPSLE)是系统性红斑狼疮的重要表现之一。以往研究主要集中在血脑屏障破坏和脑反应性自身抗体的产生上,然而,目前尚无对NPSLE进行全面的脂质组学分析。因此,本研究评估了伴有情绪障碍的NPSLE小鼠海马和肝脏的脂质组学分析,以探讨肝脑轴对该疾病的影响。
分别将MRL/lpr小鼠和MRL/mpj小鼠作为NPSLE组和对照组。在18周龄时评估小鼠的行为测试和全身疾病特征。采用超高效液相色谱-串联质谱法(UPLC-MS/MS)测定脂质代谢物。使用多变量统计分析来鉴定两组中差异表达的脂质代谢物。
我们的结果表明,NPSLE组和对照组在海马和肝脏中分别有355种和405种脂质代谢物差异表达。根据通路富集分析,有几个通路受到影响,其中甘油磷脂代谢通路与小鼠的抑郁行为最为相关。
基于UPLC-MS/MS的结果为肝脑轴如何影响NPSLE提供了证据,并增进了对NPSLE发病机制的理解。