Shanghai Institute of Rheumatology, Renji Hospital, Shanghai Jiao Tong University School of Medicine, 145 Shan Dong Road (c), Shanghai, China.
Shenzhen Futian Hospital for Rheumatic Diseases, 22 Nong Lin Road, Shenzhen, China.
Arthritis Res Ther. 2019 Sep 3;21(1):205. doi: 10.1186/s13075-019-1985-9.
Neuropsychiatric systemic lupus erythaematosus (NP-SLE) is one of the major manifestations of lupus. However, the mechanisms involved in NP-SLE are still largely unknown. The abnormal activation of the type I IFN signalling pathway is involved in SLE pathogenesis and is linked to NP-SLE, but the effect of IFN-α on NP-SLE encephalopathy has not been systematically studied.
An intravenous injection of Adv-IFN-α (10 mice, 10 × 10 vp) was administered to the IFN-α-treated group, and Adv-ctrl (10 mice, 10 × 10 vp) (ViGene Biosciences, China) was administered to the control group. Gene expression was determined by real-time quantitative polymerase chain reaction (RT-qPCR). Enzyme-linked immunosorbent assay (ELISA) was used to detect antibodies in the serum, and urinary protein levels were measured with a BCA Protein Assay kit. Haematoxylin-eosin (H&E) and periodic acid-Schiff (PAS)-light green staining were used for kidney histology. The elevated plus-maze test, novelty-suppressed feeding assay, open-field test, tail suspension test, social dominance tube test, three-chamber social interaction test, step-down passive avoidance test and novelty Y-maze task were used to assess behaviour.
In this study, we performed a series of behavioural tests to assess the neuropsychiatric phenotypes of IFN-α-treated NZB/NZW F1 mice and found that these mice developed a series of mental disorders such as anxiety-like phenotypes, depression-like phenotypes, deficits in sociability and cognitive impairments, which mimic the neuropsychiatric manifestations of NP-SLE, with a consistent onset and progression.
Our research verified that IFN-α plays a critical role in NP-SLE and provides a comprehensive NP-SLE mouse model for dissecting the mechanisms of NP-SLE and developing novel therapies for intervention.
神经精神性狼疮（NP-SLE）是狼疮的主要表现之一。然而，NP-SLE 涉及的机制在很大程度上仍然未知。I 型干扰素信号通路的异常激活与 SLE 的发病机制有关，并且与 NP-SLE 有关，但 IFN-α 对 NP-SLE 脑病的影响尚未得到系统研究。
用 Adv-IFN-α（10 只小鼠，10×10 vp）对 IFN-α 处理组进行静脉注射，用 Adv-ctrl（10 只小鼠，10×10 vp）（ViGene Biosciences，中国）对对照组进行注射。通过实时定量聚合酶链反应（RT-qPCR）测定基因表达。酶联免疫吸附试验（ELISA）用于检测血清中的抗体，用 BCA 蛋白测定试剂盒测量尿蛋白水平。苏木精-伊红（H&E）和过碘酸-Schiff（PAS）-亮绿染色用于肾脏组织学检查。高架十字迷宫试验、新奇抑制喂养试验、旷场试验、悬尾试验、社会优势管试验、三箱社交互动试验、跳下被动回避试验和新奇 Y 迷宫任务用于评估行为。
在这项研究中，我们进行了一系列行为学测试来评估 IFN-α 处理的 NZB/NZW F1 小鼠的神经精神表型，发现这些小鼠表现出一系列精神障碍，如焦虑样表型、抑郁样表型、社交能力缺陷和认知障碍，这些表现与 NP-SLE 的神经精神表现相吻合，具有一致的发病和进展。
我们的研究证实 IFN-α 在 NP-SLE 中起关键作用，并为剖析 NP-SLE 机制和开发新型干预疗法提供了一个全面的 NP-SLE 小鼠模型。
