中文摘要
IL-6/IL-6R是复杂的跨系统传导信号系统，通过不同的传导方式，在免疫应答和神经生理功能网络中发挥重要的作用。IL-6的信号传导异常可能参与精神疾病的损伤过程，课题组的相关工作也证明精神疾病患者血清中IL-6/IL-6R/sIL-6R/gp130信号链的异常表达具有高密切疾病相关性。本申请拟在前期工作的基础上，应用IL-6敲除鼠和抗体阻断sIL-6R实验鼠制备应激损伤模型，采用real-time RT-PCR、免疫组化、荧光标记、全内反射荧光显微镜成像技术、细胞表面标记技术，分析DAMP与PAMP不同识别模式下，海马脑区微环境中神经元、胶质细胞、血管内皮细胞和炎症细胞IL-6/IL-6R/sIL-6R/gp130信号传导模式，，探讨IL-6/IL-6R/sIL-6R/gp130信号通路在精神神经疾病损伤过程中的中枢调节作用，为相关疾病的机制研究、诊断、治疗和预防提供一个新的策略。
英文摘要
IL-6/IL-6R cross-system transmission signal is a very complex system .Through different conduction modes,it plays an important role in the immune response and neurophysiological function network. A large number of studies have shown that IL-6 signal transduction exception may be involved in mental disorders. Related work in our research group also proved that the abnormal expression of the IL-6/IL-6R/sIL-6R/gp130 signal chain in the serum of patients with mental illness have close correlation with the disease. This application is proposed on the basis of the preliminary work,and we use IL-6 knockout mice and antibody blocking sIL-6R to prepare stress injury model and real-time RT-PCR, immunohistochemistry, fluorescence labeling, total internal reflection fluorescence microscopy imaging technology,cell surface marker technology,so we can analysise IL-6/IL-6R/sIL-6R/gp130 signal conduction mode of neurons , glial cells, endothelial cells and the inflammatory cells in the hippocampus microenvironment under DAMP and PAMP recognition mode.We can investigate the central regulatory role of IL-6/IL-6R/sIL-6R/gp130 signaling pathways in the process of neuropsychiatric disease and provide a new strategy for the mechanisms study, diagnosis, treatment and prevention of related disease.
结题摘要
IL-6/IL-6R是复杂的跨系统传导信号系统，通过不同的传导方式，在免疫应答和神经生理功能网络中发挥重要的作用。本课题研究在前期工作的基础上，应用IL-6敲除鼠和抗体阻断sIL-6R实验鼠制备应激损伤模型，探讨IL-6/IL-6R/sIL-6R/gp130信号通路在精神神经疾病损伤过程中的中枢调节作用，获得以下结果：1） IL-1β、IL-6、TGF-β1、CRP和ACTH参与应激信号传导，其中IL-1β和IL-6的表达慢性应激组高于急性应激组；CRP和ACTH参与应激信号传导，其中急性应激组高于慢性应激组；TGF-β1急性应激组和慢性应激组较对照组均有所降低，慢性应激组低于急性应激组 ；2） IL-1β、IL-6、TGF-β1、CRP和ACTH信号在应激模型的外周血和中枢功能脑区的变化趋势与信号功能相关；3） IL-6受体敲除鼠进行IL-6/IL-6R相关信号连研究 IL-6R敲除能够使应激模型小鼠实验各组外周血中ACTH、CRP、IL-1和IL-6的表达全部降低；中枢功能相关脑区IL-1和IL-6表达也降低，原有的曲线关系表现不明显；IL-6R敲除不能使应激模型小鼠中枢脑区中功能相关伴随信号IL-1代偿性增高；4） IL-6R敲除对IL-1R下游相关信号的作用没有特异性；研究结果提示IL-6/IL-6R是复杂的跨系统传导信号系统，与IL-1协同参加复杂生理功能的传导。阻断IL-6/IL-6R信号通路可以降低功能相关刺激的信号链的信号强度，抑制模型动物的应答。