紫花香茅总黄酮调控ROCK/Claudins信号通路改善流感病毒性肺气血屏障损伤的机制研究

我国是流感疫情高发地区，目前临床常用的抗病毒药极易产生耐药性和副作用，寻找安全有效的抗流感病毒药物具有重要的社会意义和经济价值。中药通过干预流感病毒所致的气血屏障损伤，在防治流感病毒方面具独特优势。项目组前期研究已证实紫花香茅中的药效物质黄酮具有抗流感病毒、免疫调控和炎症干预作用，但其作用机制尚不明确。为阐明紫花香茅黄酮在抗肺气血屏障损伤方面的具体作用机制，本课题以ROCK介导的细胞间紧密连接蛋白为切入点，采用生物信息学和基因沉默的研究方法，从血管通透性、细胞凋亡、细胞骨架和信号转导4个方面，动态观察紫花香茅黄酮对感染细胞通透性异常的改善作用，阐明其抗流感病毒效应的信号转导机制和细胞超微结构修复机制，揭示其主要作用靶点或作用层次。该项目可为中药抗流感病毒药效靶点的发现及其作用机制研究提供理论基础，为抗流感中药的新药研发提供支持，同时对促进紫花香茅药材的产业化种植和资源开发利用具有积极作用。

There is a high incidence of influenza in China. Therefore, developing an effective and safe anti-influenza virus drug will have important social significance and great economic value, while the commonly used antiviral drugs in clinical easily generate resistance or side effects. Traditional Chinese medicine (TCM) show unique advantages against influenza virus through the intervention of influenza virus-induced pulmonary blood-gas barrier injury. It had been confirmed in our previous studies that the active constituent of Mosla Scabra-total flavonoids (MF) exerts anti-influenza virus activity, immune regulation and inhibition of inflammation, but its mechanism is still unclear. To elucidate this mechanism, amelioration of MF on abnormal permeability of influenza-infected cells were observed dynamically from the four aspects of vessel permeability, apoptosis, cytoskeleton and signal transduction, based on virus-induced gene silencing and bioinformatics methods. This investigation will reveal signal transduction mechanisms and repairing effect of MF on cell ultrastructure via ROCK/Claudins signaling pathways, and the potential therapeutic targets and action level for the development of new anti-influenza agents include MF will also been demonstrated. Meanwhile, this study not only provides theoretical foundation for drug target discovery and mechanism research of the TCM against influenza virus, but also provides support for the development of new anti-influenza drug. Moreover, planting industrialization of this medicinal plants and local resource exploitation may be promoted.