基于VIP/PKA/AQP5通路的石荠苧总黄酮抗流感病毒作用机制研究

项目名称： 基于VIP/PKA/AQP5通路的石荠苧总黄酮抗流感病毒作用机制研究

项目编号： No.81202977

项目类型： 青年科学基金项目

立项/批准年度： 2013

项目学科： 医学八处

项目作者： 余陈欢

作者单位： 浙江省医学科学院

项目金额： 24万元

中文摘要： 中医药治疗流感具有独特优势。石荠苧为江浙民间常用中药，地方标准收载药材，主治时疫感冒、风热外感等症。项目组前期证实其药效物质黄酮具有体内外抗流感病毒作用，可通过调控VIP和AQP5表达而改善病毒性病理损伤，而非对TLRs经典通路的阻断作用。为阐明这一新的药效机制，本项目以VIP/PKA/AQP5通路信号转导为切入点，通过建立流感感染小鼠模型和离体细胞模型，借用血清药理学和基因沉默的研究方法，从水液代谢、病毒抑制和信号转导3个方面，动态观察石荠苧总黄酮对感染组织水液代谢异常的调控作用，阐明其抗流感病毒效应的信号转导机制和时空变化规律，揭示其神经-免疫网络调控机制和主要作用靶点，阐明其"清肺化痰"的科学内涵，为石荠苧药材的质量评价，药效新靶点的发现，及抗流感中药新药的研发提供依据，也为中药抗流感病毒作用机制的研究提供新的思路和方法。同时对促进石荠苧药材产业化种植、提高三农经济具有积极作用。

中文关键词： 黄酮类化合物；血管活性肠肽；水通道蛋白5；细胞凋亡；炎症反应

英文摘要： Traditional Chinese medicine has unique advantages for the treatment of influenza. Mosla Scabra is widely used as a traditional medicinal herb in Jiangsu-Zhejiang region and is regulated in local standards. It is often used as an antipyretic and antiviral drug for lung diseases and has been found to be effective in colds, fever and influenza. In our past researches, we found that its active constituents- - total flavonoids (MF) exhibit anti-influenza virus activities in vivo and in vitro. In particular, MF could ameliorate viral pathological damage through up-regulation of VIP and AQP5 expressions instead of the inhibition of canonical TLRs signal pathway. To clarify this new mechanism, this research, taking VIP/PKA/AQP5 pathways as the breakthrough point, is to investigate its accommodation on abnormal developing water metabolism, and to observe its signal transduction mechanism and spatial variation regularity by using gene silencing and serum pharmacology methods in lethal murine experimental influenza virus infection model and in vitro cell model. This research also reveals regulatory mechanism of MF in the neuro-immune network and major targets to expound its "ventilating lung and eliminating phlegm" scientific connotation from water metabolism, viral load and signal transduction. It not only provides evide

英文关键词： Flavonoids；Vasoactive intestinal peptide；Aquaporin 5；Cell apoptosis；Inflammation