NGF介导的神经源性炎症在子宫内膜异位症发生机制中的作用研究

Endometriosis (EMs) seriously affected the patient s ' physical and mental health. But the pathophysiology of endometriosis is still poorly understood now. Elucidating the pathogenesis of EMs is very helpful to early diagnosis and therapy. Preliminary studies of our group found that nerve fibers， nerve growth factor (NGF) and its receptors were abnormally elevated in the EMs lesions, and NGF is well known to play a key role in the regulation of immune and inflammatory. Therefore we speculated that EMs may be a neurological inflammatory disease, and NGF may be the important regulatory factors in pathogenesis of EMs. This project first cultured monocyte-macrophage cells in vitro, then validate the regulatory role of NGF on secretion of inflammatory cytokines in macrophages. Lentiviral technology was used to establish rat model of peritoneal partial suppression or overexpression of NGF, to verify that the role of NGF-mediated inflammatory cytokines in the pathogenesis of EMs. Peritoneal fluids of EMs patients were collected to detect the concentration of NGF and IL-6, IL-8 and TNF-α in clinical field. Finally, the main signal transduction pathways involved in NGF-mediated inflammatory factors secretions of monocyte-macrophage cells were studied. MicroRNA and their target genes involved in NGF regulatory system were investigated, too. This research project we proposed not only verifies the mechanism of EMs occurrence, but also provides new ideas and therapeutic targets for diagnosis and treatment of EMs.

子宫内膜异位症（EMs）严重影响患者身心健康，但发病机制目前还不清楚。本课题组前期研究发现EMs病灶中神经纤维、神经生长因子（NGF）及其受体异常升高，已知NGF在免疫炎症调节中发挥重要作用。因此推测EMs可能是一种神经炎症性疾病，NGF可能是EMs发生的重要调控因素。本项目拟通过体外和体内实验以验证NGF对巨噬细胞分泌炎症因子的调节作用；通过慢病毒技术，建立NGF低表达和过表达的EMs模型鼠，验证NGF介导的炎症因子在EMs发病机制中的作用；检测EMs患者腹腔液中NGF和IL-6、IL-8以及TNF-α的浓度相关性；研究NGF介导单核巨噬细胞产生炎症因子的主要信号传导通路，以及NGF调控单核巨噬细胞过程中涉及的主要microRNA分子及其靶基因与信号通路的关系，从而完整的了解NGF的下游调控网络。本项目预期结果可对EMs的发生机制作出初步解释，也为EMs的诊断和治疗提供新的思路和治疗靶点

子宫内膜异位症（EMs）严重影响患者身心健康，但发病机制目前还不清楚。本课题组前期研究发现EMs病灶中神经纤维、神经生长因子（NGF）及其受体异常升高，已知NGF在免疫炎症调节中发挥重要作用。因此推测EMs可能是一种神经炎症性疾病，NGF可能是EMs发生的重要调控因素。本项目通过体外和体内实验以验证NGF对巨噬细胞分泌炎症因子的调节作用；通过基因枪轰击技术，建立NGF局部低表达EMs模型鼠，验证NGF介导的炎症因子在EMs发病机制中的作用，进一步通过转录组学分析探究了NGF与单核细胞来源的巨噬细胞之间的相互作用，从而完整的了解NGF的在EMs中的作用机制。本项目首次研究了腹腔巨噬细胞新分型在EMs中的数量和功能变化情况，发现腹腔大巨噬细胞和腹腔小巨噬细胞在EMs中不同作用。本项目的结果对EMs的发生机制作出初步解释，也为EMs的诊断和治疗提供新的思路和治疗靶点。