Transcriptomes in the Sciatic Nerves of Lewis Rats with Experimental Autoimmune Neuritis

Guillain-Barré syndrome (GBS) is characterized by acute immune-mediated peripheral neuropathy, which may result in rapidly progressive paralysis and fatal respiratory failure. As the underlying pathological mechanisms of GBS are unclear, we surveyed the transcriptome of rats with experimental autoimmune neuritis (EAN), a model of GBS. Briefly, sciatic nerves on both sides were collected from 8–10-week-old Lewis rats during early (10 days post-induction), peak (19 days), and late neuritis (30 days). Total RNA was sequenced to identify differentially expressed genes. Compared to control rats without induced neuritis, 33 genes were differentially expressed in the early phase (14 upregulated and 19 downregulated), with an adjusted P-value < 0.05 and |log2 fold-change| > 1, as were 137 genes in the peak phase (126 upregulated and 11 downregulated) and 60 genes in the late phase (58 upregulated and 2 downregulated). Eleven of these genes were common to all stages, suggesting their crucial roles throughout the disease course. Analysis of protein-protein interactions revealed Fos, Ccl2, Itgax and C3 as node genes at different stages. Functional analysis of differentially expressed genes identified biological processes and pathways that are activated as neuritis progresses. This is the first genome-wide gene expression study of peripheral nerves in experimental autoimmune neuritis model. Dynamic gene expression and significantly altered biological functions were detected in different phases of the disease, increasing our understanding of the molecular mechanisms underlying EAN and highlighting potential targets for its diagnosis and treatment.吉兰-巴雷综合征（Guillain-Barré Syndrome, GBS）是一类以急性免疫介导性周围神经病为核心特征的疾病，可引发快速进展性瘫痪乃至致死性呼吸衰竭。由于该病的潜在病理机制尚未明确，我们针对吉兰-巴雷综合征的动物模型——实验性自身免疫性神经炎（experimental autoimmune neuritis, EAN）大鼠的转录组展开了研究。 实验流程简述如下：于诱导后早期（造模后10天）、高峰期（造模后19天）与晚期神经炎阶段（造模后30天），从8~10周龄的Lewis大鼠体内采集双侧坐骨神经；随后提取总RNA并进行测序，以筛选差异表达基因。 与未诱导神经炎的对照大鼠相比，在校正后P值<0.05且|log₂倍变化值|>1的标准下，早期阶段共有33个基因呈现差异表达（14个上调、19个下调）；高峰期有137个差异表达基因（126个上调、11个下调），晚期阶段则有60个（58个上调、2个下调）。其中11个基因在所有疾病阶段均存在差异表达，提示它们在整个病程中发挥关键调控作用。 蛋白质相互作用分析结果显示，Fos、Ccl2、Itgax与C3为不同疾病阶段的核心节点基因。对差异表达基因的功能分析表明，随着神经炎病情进展，诸多生物学过程与信号通路被激活。 本研究是首个针对实验性自身免疫性神经炎模型的周围神经全基因组基因表达研究。本研究在疾病不同阶段均检测到动态变化的基因表达模式与显著改变的生物学功能，这加深了我们对EAN潜在分子机制的理解，同时为该病的诊断与治疗指明了潜在靶点。