呼吸道M细胞及黏膜RIG-I/MAVS/IRF3/7信号通路触发的天然免疫应答对肾阳虚外感病证的调控作用及经方干预机制研究

流感是流感病毒引起的急性呼吸道传染病，对其高危人群防治一直是现代医学亟待解决难题，此类人群多属于中医“肾阳虚外感证”。我们依据大量研究证据推测，肾阳虚外感证是因机体免疫力低下后流感病毒首先集中侵染到咽喉部位呼吸道M细胞，导致相应黏膜免疫RIG-I受体应答失常，产生过量炎性因子触发级联放大效应而造成机体严重病理损伤。本课题病证结合，在前期已建立成熟肾阳虚外感小鼠模型（苯甲酸雌二醇腹腔注射，鼻腔感染H1N1/rPR8-GFP流感病毒）基础上，从呼吸道M细胞、RIG-I受体重要的效应细胞和分子入手，研究转录因子IRF3/7，下游I型干扰素及TNF-alpha、IL-6、IL-10等促炎和抗炎细胞因子mRNA和蛋白水平表达；并以麻黄细辛附子汤（MXF）干预RIG-I受体所触发天然免疫应答通路，探讨MXF对黏膜免疫调控途径与机制。深入研究该免疫应答在肾阳虚外感证发病的始动和关键环节及MXF干预靶点。

Influenza is an acute respiratory infectious disease caused by influenza virus. The prevention and treatment of influenza in high risk population which susceptible to influenza is always urgent problem to be solved in modern medicine, and this kind of syndrome belongs to Kidney-yang deficiency with exterior symptom according to traditional Chinese medicine. Based on lots of research evidences, we hypothesis that Kidney-yang deficiency with exterior symptom is a kind of influenza virus infection at throat part respiratory M cells in the immunodeficiency condition firstly, then to have response disorder with corresponding mucosal immunity RIG-I receptor, causing cascaded amplification effect triggered by excess inflammatory factors and serious pathologic injury. Mouse model of Kidney-yang deficiency with exterior symptom has been established by our research group through intraperitoneal injection with benzoic acid estradiol combined with intranasal instillation of the H1N1/rPR8-GFP virus. We will start with important effect cell and molecular from respiratory M cells and RIG-I receptor, studying the expression of mRNA and protein with transcription factor IRF3/7, type I interferon, TNF-alpha, IL-6, IL-10 etc. Mahuang-xixin-fuzi decoction would be used for intervention with RIG-I receptor which triggers natural immune response pathway, and mucosal immunity regulation pathway and mechanism will be investigated. Key link to the onset of Kidney-yang deficiency with exterior symptom and the target of MXF in this immunity response will be explored further in the project.