miR-511-3p介导PI3K/AKT/mTOR通路调控巨噬细胞极化在过敏性哮喘中的作用及加味玉屏风散干预机制研究

Macrophage polarization has been shown to have a profound impact on allergic asthma pathogenesis. MiR-511-3p can modulate macrophage polarization and alleviate the allergen-induced lung inflammation, and PI3K/AKT/mTOR is an important signal pathway regulating macrophage polarization. Modified Yupingfeng Powder can reduce the airway inflammation and improve the symptoms of allergic asthma, but its mechanism has not been clarified. Our previous study found that levels of plasma miR-511-3p were significantly higher in allergic asthmatic patients after treatment with modified Yupingfeng Powder compared with those before treatment, and PIK3R3 was the target gene of miR-511-3p. It is suggested that modified Yupingfeng Powder may regulate macrophage polarization through miR-511-3p-mediated PI3K/AKT/mTOR pathway and alleviate allergen-induced lung inflammation. We will investigate the role of PI3K/AKT/mTOR pathway in the regulation of macrophage polarization by miR-511-3p in vitro and in vivo. Furthermore we explore whether miR-511-3p is involved in the protective function of modified Yupingfeng Powder on asthma, and verify whether the function is achieved through PI3K/AKT/mTOR pathway. This study will provide theoretical basis for the treatment of allergic asthma with modified Yupingfeng Powder.

巨噬细胞极化在过敏性哮喘发病中起重要作用。研究发现，miR-511-3p可通过影响巨噬细胞极化状态抑制变应原诱发的肺部炎症，而PI3K/AKT/mTOR是调控巨噬细胞极化的重要信号通路。加味玉屏风散治疗过敏性哮喘在临床上取得良好疗效。我们前期研究发现，加味玉屏风散提高哮喘患者血浆miR-511-3p水平；且PIK3R3是miR-511-3p作用靶基因。提示加味玉屏风散可能通过miR-511-3p介导的PI3K/AKT/mTOR信号通路调控巨噬细胞极化，减轻变应原诱发的肺部炎症。我们通过体内外实验，研究PI3K/AKT/mTOR信号通路在miR-511-3p调控巨噬细胞极化中的作用；并探讨加味玉屏风散对哮喘的保护作用是否有miR-511-3p参与，验证该作用是否通过PI3K/AKT/mTOR信号通路来实现。为临床应用加味玉屏风散治疗过敏性哮喘提供理论依据。

过敏性哮喘是全球最常见的慢性呼吸系统疾病，严重威胁公众健康。巨噬细胞极化在过敏性哮喘发病中起重要作用。研究发现，miR-511-3p可通过影响巨噬细胞极化状态抑制变应原诱发的肺部炎症，而PI3K/AKT/mTOR是调控巨噬细胞极化的重要信号通路。前期研究发现，加味玉屏风散提高哮喘患者血浆miR-511-3p水平；且PIK3R3是miR-511-3p作用靶基因。本研究拟通过体内外实验，观察PI3K/AKT/mTOR信号通路在miR-511-3p调控肺巨噬细胞极化和肺部炎症反应中的作用；并基于miR-511-3p/PI3K/AKT/mTOR通路，探讨加味玉屏风散对哮喘的保护作用是否有miR-511-3p参与，验证该作用是否通过PI3K/AKT/mTOR信号通路来实现。为临床应用加味玉屏风散治疗过敏性哮喘提供理论依据。本研究按计划完成体外研究，通过体外转染技术双向调节miR-511-3p表达，发现PI3K/AKT/mTOR通路在miRNA-511-3p调控巨噬细胞极化中起重要作用。并利用前期已建立的过敏性哮喘小鼠模型，采用miR-511-3p过表达技术，证实miR-511-3p通过PI3K/AKT/mTOR通路影响巨噬细胞极化状态，抑制变应原诱发的肺部炎症，在预防哮喘发生中起重要作用。但在加味玉屏风散干预治疗过敏性哮喘的机制研究中，未发现治疗前后PI3K/AKT/mTOR磷酸化有显著性差异，未能确定加味玉屏风散对哮喘的治疗作用是通过miR-511-3p介导的PI3K/AKT/mTOR信号通路来实现的。