基于肺-肠稳态探讨固本防哮饮防治儿童哮喘的机制

Gubenfangxiao decoction (GBFXD), prescribed by renowned TCM pediatrician-Jiang Yuren, achieves the outcomes of tonifying lung and consolidating the superficial, and strengthening the spleen and reducing phlegm. A cohort study indicated that GBFXD could ameliorate the constitution of children in asthma remission stage. Recent studies have demonstrated that the airway epithelium barrier dysfunction and the lung-gut mucosal immunity imbalance are crucial in inducing the recurrence of asthma. Protective immunoglobulin A (IgA), the predominant antibody at lung and gut mucosal surfaces, which can be modulated by the gut flora. Therefore, it may be meaningful to elucidate the IgA CSR-mediated mucosal immunity homeostasis in connecting the “lung-gut axis” of asthma. Our previous research showed that GBFXD might exert some effects on protecting airway epithelium integrity by inhibiting the activation of ER stress responses and upregulating the expression of SERCA pumps. Moreover, GBFXD exhibits a regulatory effect on IgA CSR-mediated gut mucosal immunity.However, our understanding of the underlying correlation between lung-gut homeostasis and the GBFXD’s therapy is limited. Based on the methods of air-liquid interface culture, laser confocal scanning microscopy techniques and 16Srna sequencing, the aim of the present study is to determine the impacts of GBFXD on airway epithelium integrity, lung-gut mucosal immunity and flora homeostasis in a murine asthma remission model.

“固本防哮饮”是名老中医江育仁教授经验方，具有“补肺固表、健脾化痰”的作用。临床研究证实该方治疗儿童哮喘安全有效。现代研究表明气道上皮完整性的破坏和肺-肠黏膜免疫失衡是哮喘反复发作的重要原因。IgA是肺-肠黏膜免疫间重要的连接者，深入研究IgA CSR调节的黏膜免疫可能是打开哮喘“肺-肠轴”效应机制的钥匙。前期实验研究发现该方可能具有通过调节内质网应激状态、提高受损钙泵表达而保护气道上皮完整性的作用；以及调节IgA CSR介导的肠道黏膜免疫的功能。据此，我们提出假说：保护气道完整性与维持肠道黏膜免疫和菌群平衡，进而调节肺-肠稳态可能与该方“补肺固表、健脾化痰”的治疗作用有关。本课题拟采用气液相界面培养、激光扫描共聚焦显微技术、细菌16SrDNA测序技术等，从气道上皮完整性、肺-肠黏膜免疫功能与菌群平衡研究固本防哮饮对哮喘肺-肠稳态的影响，探讨其“补肺固表、健脾化痰”治法的机制。

现代研究表明气道上皮完整性的破坏和肺-肠黏膜免疫失衡是哮喘反复发作的重要原因。本研究发现固本防哮饮可减轻哮喘小鼠气道炎症，增强上皮修复损伤能力，维持气道上皮结构的完整性，恢复气道上皮屏障功能，从改善呼吸道通气和换气功能和修复呼吸道上皮屏障功能损伤两个方面，初步阐述中医学治疗哮喘“益气固表”法潜在的分子生物学机制。另外，发现固本防哮饮可调节肺巨噬细胞分泌BAFF，增加肺肠IgA+B细胞活化、降低脾脏IgE+B细胞活化，并可增加小鼠结肠中产SCFAs细菌的相对比例，靶向“肠道菌群-乙酸-Tregs”轴调节肺肠黏膜免疫，从而达到“健脾化痰”的目的。