固本防哮饮防治哮喘儿童食物过敏的机制研究

In recent years, childhood asthma has increased dramatically in prevalence with a long-term clinical course. Defending against recurrence of asthma should be regarded as the promising therapeutic goal in management. Food allergy, which can cause many respiratory symptoms, is a high risk of asthma attack. Traditional Chinese medicine believes that the treatment of food allergy from "spleen and stomach" is the key to improve the constitution and reduce the recurrence of asthmatic children. Gubenfangxiao decoction (GBFXD), prescribed by renowned TCM pediatrician-Jiang Yuren, achieves the safety and efficacy outcomes and improves the digestive function of asthmatic children in remission stage, suggesting that GBFXD may exert effects by restraining food allergic reaction and preventing the recurrence of asthma. It has been noted that the disruption of epithelial cell barrier and the Treg/Th17 imbalance mediated by CCR9+ T lymphocytes are two important mechanisms in lung-gut axis during the exacerbation of asthmatic airway inflammation caused by food allergens. Previous studies suggest that GBFXD may exert anti-asthmatic effects by protecting airway epithelium integrity and adjusting Treg/Th17 immune balance mediated by gut homing CCR9. Nonetheless, it has aroused a question that whether GBFXD exerts similar outcomes in the process of food allergy induced asthma has not been studied. Based on the hypothesis that GBFXD may exert some anti-asthmatic effects by alleviating food allergy, the aim of the present study is to determine the impacts of GBFXD on the airway or the intestinal epithelium integrity and the migration of CCR9+ T lymphocytes in a food allergen-induced murine asthma model.

儿童哮喘具有发病率高、病程迁延的特点，控制哮喘复发是临床防治的重点。食物过敏可引起诸多呼吸道症状，是哮喘反复诱发的重要因素。中医认为从“脾胃论治”食物过敏，是改善哮喘患儿体质，减少复发的关键。“固本防哮饮”是名老中医江育仁教授经验方，治疗缓解期哮喘儿童安全有效，并可改善患儿的脾胃功能，提示复方可能具有调节食物过敏反应进而防治哮喘复发的作用。据报道，上皮细胞屏障损伤以及CCR9介导的Treg/Th17免疫失衡是食物过敏加剧哮喘过程中肺肠联系的重要机制。项目组已有研究及预实验提示固本防哮饮具有保护哮喘气道上皮完整性，调节肠道CCR9介导Treg/Th17平衡的作用，但对食物过敏诱发哮喘过程中的类似作用，尚未研究。据此，本课题拟从修复肺肠上皮完整性与调节食物过敏原激活的CCR9+ T淋巴细胞向肺迁移两方面，明晰固本防哮饮改善哮喘患儿易于食物过敏的体质状态，进而抑制过敏性气道炎症的机制。

儿童哮喘具有发病率高、病程迁延、易反复的特点，控制哮喘复发是临床防治的重点。哮喘儿童常伴发食物过敏表现，食物过敏可引起诸多呼吸道症状，是诱发哮喘反复的重要因素。因此，改善食物过敏状态有助于减少哮喘复发，提高患儿生存质量。中医认为从“脾胃论治”食物过敏，是改善哮喘患儿体质，减少复发的关键。“固本防哮饮”是名老中医江育仁教授经验方，治疗缓解期哮喘儿童安全有效，并可改善患儿的脾胃功能，提示复方可能具有调节食物过敏反应进而防治哮喘复发的作用。基于以上背景，本项目主要开展中药复方固本防哮饮对哮喘合并食物过敏的机制研究。研究主要结果发现：（1）利用卵清蛋白经气道和食道联合致敏构建的哮喘合并食物过敏小鼠模型，相较单纯气道致敏组气道炎症表现更为明显。（2）同时，哮喘相关炎症因子表达在食物过敏组中更高，说明食物过敏可加重全身或气道炎症表现。（3）我们也观察到气道与肠道上皮复合物表达下降，肠道上皮通透性指示物NAO水平升高，说明气道与肠道上皮屏障出现了不同程度的损失，尤以食物过敏组小鼠更严重。（4）食物过敏加重哮喘气道炎症可能与肠道固有趋化因子受体9（CCR9）水平升高，进而引起的肠道T淋巴细胞向肺迁移有关。以上反应在固本防哮饮干预后，均可得到改善或抑制，说明复方具有降低哮喘合并食物过敏小鼠肠道CCR9+T淋巴细胞向肺迁移，进而减轻哮喘慢性气道炎症和食物过敏反应的作用。