外泌体源性miRNAs在吉兰-巴雷综合征诊断和治疗中的应用研究

Guillain-Barré syndrome (GBS) is the most common and most severe acute paralytic autoimmune peripheral neuropathy in neurology. The current diagnosis depends mainly on clinical manifestations, electrophysiology and cerebrospinal fluid examination. Lack of specific diagnostic indicators is seriously affecting the patient's early diagnosis and prognosis. In addition, the current treatment of the disease is reducing the symptoms and supportive. No specific treatment is available so far. It is therefore necessary to find new biomarkers for early diagnosis and specific methods for effective treatment. Exosomal miRNAs have a wide range of biological properties and targeted specificity in the nervous system and have good resistance to degradation, therefore they are considered to be the most likely biomarkers and therapeutic targets. This study has three purposes: ①Screening for exosomal miRNA biomarkers in patients with GBS; And②Screening of possible exosomal miRNA biomarkers using the GBS animal models. ③To explore the therapeutic effect of exosomal miRNAs in GBS animal models. We hope 3-5 specific exosomal miRNA biomarkers in plasma and cerebrospinal fluid can be screened out for early diagnosis of GBS patients and to find new ways to treat GBS patients with exosomal miRNAs.

吉兰-巴雷综合征（Guillain–Barré syndrome，GBS）是神经科最常见且最严重的急性麻痹性自身免疫性周围神经病。外泌体源性的miRNAs在神经免疫系统具有广泛的生物学特性和靶向特异性，且具有良好的抗降解能力，因此目前被认为是最有可能的生物标记物和治疗靶点。本研究有三个目的：①在临床诊断为GBS的病人中验证筛选的外泌体源性的miRNA生物标记物。②利用GBS动物模型筛选可能的外泌体源性的miRNA生物标记物。③在GBS动物模型中探索外泌体源性miRNA的治疗作用。我们希望能够在血浆和脑脊液中筛选出3-5个特异性的外泌体源性miRNA标记物，用于GBS病人的早期诊断，并找到利用外泌体源性miRNA治疗GBS病人的新方法。

吉兰-巴雷综合征（Guillain-Barré syndrome，GBS）是神经科最常见且最严重的急性麻痹性自身免疫性周围神经病。外泌体源性的miRNAs在神经免疫系统具有广泛的生物学特性和靶向特异性，且具有良好的抗降解能力，因此目前被认为是最有可能的生物标记物和治疗靶点。本项目的研究目标是在外泌体源性miRNAs 中筛选出可用于GBS 早期诊断的生物标记物并探讨外泌体能否作为GBS 特异性的治疗方法。我们首先收集了94例GBS患者（脱髓鞘型44例、轴索型32例和不能分类型18例）外周血清标本并进行了外泌体的分离，将所得外泌体进行miRNA表达谱的分析；筛选出差异性表达的miRNA；然后建立了GBS的脱髓鞘型和轴索型动物模型，分别在模型发病后的不同时间点收集血清中外泌体进行miRNA表达谱的分析，比较人类GBS与动物模型中miRNA表达谱的差异，结果显示：人类GBS与动物模型中的miRNA表达谱并不一致，其原因应为种属差异造成；我们还进一步观察了外源性刺激对于树突状细胞和巨噬细胞分泌外泌体中miRNA表达谱的差异以及这些外源性刺激后产生的外泌体对GBS动物模型的治疗作用。本项目中我们系统的研究了GBS及其对照外周血清中miRNA表达谱，下一步如果在更大样本量GBS人群中能验证这些差异性表达的miRNA，将为GBS的早期诊断提供了新的生物标志物。