基于肺-肠轴探讨金欣口服液对RSV感染诱发哮喘急性加重小鼠的干预作用

The interior-exterior relation between lung and large intestine theory in Traditional Chinese Medicine and the lung-gut axis in modern research all emphasize the lung has close relations to intestine. In previous studies，it has been shown that Jinxin Oral Liquid is effective for RSV-induced respiratory tract infection. However, the mechanism remains unclear due to the multi-target effects of Chinese Medicine. This study, based on the Lung-gut axis, is to discuss the relationship between RSV-induced exacerbations in a mouse model of asthma and gut microbiota, short-chain fatty acid（SCFA）, immune system，as well as the intervention of Jinxin Oral Liquid. Samples of feces, blood, bronchoalveolar lavage fluid and lung tissue are analyzed by using target metabolomics and molecular biology approaches. The changes of above samples are analyzed to establish the relationship between RSV-induced exacerbations in asthma and gut microbiota-microbiota metabolites-pulmonary immune system. This project also discusses the effect of Jinxin Oral Liquid on above items in the mouse model and its potential mechanism. Eventually, based on the lung-gut axis theory, the effect of Jinxin Oral Liquid on RSV-induced exacerbations in asthma can be expounded, which may enhance our understanding of the childhood asthma’s pathogenesis and its treatment. The findings are also expected to give insights into scientific essence of the interior-exterior relation between lung and large intestine.

中医学“肺与大肠相表里”理论以及现代研究“肺-肠轴”学说均提示肠道与肺之间的密切联系。前期研究已证实金欣口服液是治疗RSV引起的呼吸道感染的有效药物。鉴于中药复方作用的多靶点性，本课题拟基于“肺-肠轴”探讨RSV感染诱发哮喘急性加重小鼠模型中肠道菌群、短链脂肪酸、免疫细胞和免疫活性因子之间的关系及金欣口服液的干预作用。运用靶向代谢组学及分子生物学相关实验方法对粪便、血液、肺泡灌洗液、肺组织等样本进行分析，了解肠道菌群、短链脂肪酸、免疫细胞和免疫活性因子的变化，建立肠道微生物-微生物代谢产物-肺部免疫和RSV诱发哮喘急性加重之间的联系。同时探索金欣口服液通过影响肠道菌群引起短链脂肪酸含量变化进而调节肺部免疫以缓解RSV诱发哮喘急性加重的可能机制，最终通过“肺-肠轴”阐明金欣口服液对RSV诱发哮喘急性加重的干预作用，为研究哮喘发病机制和治疗提供新的思路,也为“肺与大肠相表里”理论提供科学依据。

中医学“肺与大肠相表里”理论以及现代研究“肺-肠轴”学说均提示肠道与肺之间的密切联系。前期研究已证实金欣口服液是治疗RSV引起的呼吸道感染的有效药物。鉴于中药复方作用的多靶点性，本课题通过靶向代谢组学及分子生物学相关实验方法分别检测RSV感染诱发哮喘急性加重小鼠模型及金欣口服液干预后肠道菌群、SCFA、HDAC活性、Treg等相关免疫细胞和总IgE等免疫活性分子的改变。本项目发现RSV感染诱发哮喘急性加重模型中肠道菌群与正常组存在差异，血液循环中乙酸、丁酸等SCFA含量明显降低，进而抑制Treg细胞并过度分泌IgE等相关免疫活性因子。而金欣口服液主要通过影响肠道菌群上调乙酸、丁酸等SCFA含量，进而逆转模型组Treg细胞的降低和总IgE等免疫活性分子的过度分泌，从而通过“肺-肠轴”阐明金欣口服液对RSV诱发哮喘急性加重的干预作用，为研究哮喘发病机制和治疗提供新的思路，也为“肺与大肠相表里”理论提供科学依据。