基于肝肺相关理论探讨哮喘宁颗粒调控PNEC–ILC2神经免疫模块干预心理应激哮喘的机制研究

心理应激哮喘是支气管哮喘的重要表型，目前仍缺乏有效治疗药物。课题组证实，具有调肝理肺功效的哮喘宁颗粒临床疗效显著，且能抑制心理应激哮喘大鼠肺部Th2免疫炎症，但机制不明。肺神经内分泌细胞（PNEC）与2型固有淋巴细胞（ILC2）介导的Th2免疫炎症是心理应激哮喘的病理基础，其发病机制与中医肝肺相关理论契合。基于此，提出“哮喘宁颗粒通过调控PNEC–ILC2神经免疫模块，进而抑制Th2免疫炎症，控制心理应激哮喘发作及加重”的科学假说。本项目拟建立心理应激哮喘大鼠模型并序贯培养PNEC和ILC2，通过检测肺功能等指标评价哮喘宁颗粒对模型大鼠的治疗作用，运用WB、RT‒qPCR等技术分析其对AChR、CGRP、CGRPR、IL-13等PNEC–ILC2神经免疫模块指标以及IL-4、IL-5等Th2免疫炎症指标的影响，揭示其作用靶点及机理，阐明调肝理肺法的科学内涵，为肝肺相关理论提供依据。

The psychological stress asthma is a crucial phenotype of bronchial asthma, with no effective therapeutic drug for at present. The research team confirmed that Xiaochuanning Granule, with the effect of regulating the liver and lung, was effective in the treatment of asthma and could inhibit Th2 immune inflammation in the lungs of model rats with psychological stress asthma, but the mechanism is still unknown. The Th2 immune inflammation mediated by pulmonary neuroendocrine cell (PNEC) and type 2 intrinsic lymphocytes (ILC2) is the pathogenesis of psychological stress asthma, whose mechanism conforms to the liver-lung related theory of Traditional Chinese Medicine. Based on the previous researches, our group puts forward the scientific hypothesis that “Xiaochuanning Granule can inhibit the Th2 immune inflammation and control the attack and exacerbation of psychological stress asthma by regulating PNEC-ILC2 neuroimmune module”. This project intends to establish the rat model with psychological stress asthma and the sequential PNEC and ILC2 cells culture. The therapeutic effect of Xiaochuanning Granule on model rats will be evaluated by the pulmonary function test. Furthermore, both the PNEC-ILC2 neuroimmune module indexes, such as AChR, CGRP, CGRPR and IL-13, and Th2 immune inflammation indexes, such as IL-4 and IL-5, will be analyzed by means of WB, RT-qPCR techniques, etc. This project aims to reveal the targets and mechanism of Xiaochuanning Granule, clarify the scientific connotation of the method of modulating the liver and lung, and provide the basis for the liver-lung related theory.