Guo D D, Hu B, Tang H Y, Sun Y Y, Liu B, Tian Q M, Bi H S
Shandong Provincial Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases, Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Therapy of Ocular Diseases in Universities of Shandong, Eye Institute of Shandong University of Traditional Chinese Medicine, Jinan, China.
Affiliated Eye Hospital of Shandong University of Traditional Chinese Medicine, Jinan, China.
Scand J Immunol. 2017 May;85(5):331-342. doi: 10.1111/sji.12539.
Uveitis is an autoimmune disease that usually damages the vision function, leading to poor visual quality in patients. As an autoimmune ocular inflammatory disease, the pathogenesis of uveitis is associated with abnormal expression of some proteins and aberrant regulation of multiple signalling pathways. Nevertheless, the detailed mechanism remains unclear. In this study, we induced an experimental autoimmune uveitis (EAU) model in rats. We determined the levels of C3a and membrane attack complex C5b-9 (soluble C5b-9, sC5b-9) in both plasma and aqueous humour, identified the differentially expressed proteins in plasma by liquid chromatography-tandem mass spectrometry and employed bioinformatics algorithms to analyse differentially expressed proteins in EAU rat plasma. The results demonstrate that there were 168 differentially expressed plasma proteins in EAU rats versus control subjects. The levels of sC5b-9 and C3a were elevated in the plasmas and aqueous humours of EAU rats. Gene ontology enrichment analysis showed that the differentially expressed proteins in EAU rat plasma were mainly involved in metabolic and immune processes. Kyoto encyclopedia of genes and genomes (KEGG) pathway annotation, database for annotation, visualization and integrated discovery (DAVID) and protein-protein interaction analyses revealed that the differentially expressed proteins in EAU rat plasmas were closely associated with complement and coagulation cascades, metabolic pathways, NF-kappa B, PI3K-Akt, Toll-like receptors and autophagy. Overall, the differentially expressed proteins in EAU rat plasmas are mainly involved in the complement and coagulation cascades. The pathogenesis of uveitis closely correlates with complement activation.
葡萄膜炎是一种自身免疫性疾病，通常会损害视力功能，导致患者视觉质量下降。作为一种自身免疫性眼部炎症性疾病，葡萄膜炎的发病机制与某些蛋白质的异常表达和多种信号通路的异常调节有关。然而，具体机制仍不清楚。在本研究中，我们在大鼠中诱导了实验性自身免疫性葡萄膜炎（EAU）模型。我们测定了血浆和房水中C3a和膜攻击复合物C5b-9（可溶性C5b-9，sC5b-9）的水平，通过液相色谱-串联质谱法鉴定了血浆中差异表达的蛋白质，并采用生物信息学算法分析了EAU大鼠血浆中差异表达的蛋白质。结果表明，与对照相比，EAU大鼠有168种差异表达的血浆蛋白。EAU大鼠的血浆和房水中sC5b-9和C3a水平升高。基因本体富集分析表明，EAU大鼠血浆中差异表达的蛋白质主要参与代谢和免疫过程。京都基因与基因组百科全书（KEGG）通路注释、注释、可视化和综合发现数据库（DAVID）以及蛋白质-蛋白质相互作用分析显示，EAU大鼠血浆中差异表达的蛋白质与补体和凝血级联、代谢途径、核因子κB、磷脂酰肌醇3-激酶-蛋白激酶B（PI3K-Akt）、Toll样受体和自噬密切相关。总体而言，EAU大鼠血浆中差异表达的蛋白质主要参与补体和凝血级联。葡萄膜炎的发病机制与补体激活密切相关。
