目的 运用网络药理学的分析方法，探讨小儿消积止咳口服液（Pediatric Xiaoji Zhike Oral Liquid，PXZOL）治疗小儿食积咳嗽的功效网络与作用机制。方法 通过Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform（TCMSP）、Traditional Chinese Medicine Information Database（TCM-ID）等数据库并结合文献，分别搜集PXZOL中药味的主要成分及其作用靶点。利用Comparative Toxicogenomics Database（CTD）、PubMed、Drugbank等数据库并结合文献搜集功能性便秘相关靶点。通过Cytoscape 3.6.0软件构建PXZOL的药味-成分-靶点网络和药物-靶点-疾病的蛋白相互作用（protein-protein interaction network，PPI）网络。通过对PPI网络中靶点进行筛选，构建核心靶点网络。运用ClueGO插件对核心靶点网络进行Gene Ontology（GO）分析和Pathway分析。利用BioGPS数据库对核心靶点进行器官定位。结果 GO分析结果显示，PXZOL发挥止咳作用主要是通过调节核转录因子-κB（nuclear transcription factor-κB，NF-κB）信号传导来实现。而发挥消积作用主要是通过相关蛋白质的合成和调节对刺激反应来实现。Pathway分析结果显示，PXZOL发挥止咳作用主要通过丝裂原活化蛋白激酶（mitogen-activated protein kinase，MAPK）信号通路、视黄酸（维甲酸）诱导基因蛋白I（retinoic acid-inducible gene-I，RIG-I）样受体信号通路、白细胞介素17（interleukin 17，IL17）信号通路、肿瘤坏死因子受体相关因子6（TNF receptor associated factor 6，TRAF6）介导NF-κB激活等通路。发挥消积作用主要通过多种免疫和炎症信号传导通路来实现。器官定位方面，止咳作用靶点、消积作用靶点以及其共同靶点均有近50%靶点在肺和大肠上有较多表达。结论 PXZOL是基于中医“肺与大肠相表里”的理论而组方潜药，现代药理学研究表明发挥“消积止咳”作用多集中在免疫和炎症方面，网络药理学研究发现止咳和消积的作用靶点以及其共同靶点在肺和大肠上有较多表达的数量近50%，从主治疾病和作用网络上提示，PXZOL的疗效发挥是通过黏膜免疫与炎症介导路径来体现中医“肺与大肠相表里”理论的科学性，也为后续在小儿食积咳嗽模型和临床进一步深入研究和验证奠定基础。

Objective Using network pharmacology analysis method to explore the efficacy network and mechanism of Pediatric Xiaoji Zhike Oral Liquid (PXZOL) in treating children with food accumulation cough. Methods We collected main components in PXZOL and their targets by using Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform (TCMSP) and Traditional Chinese Medicine Information Database (TCM-ID) combined with literature. Functional constipation related targets were searched from Comparative Toxicogenomics Database (CTD), PubMed, Drugbank, and other databases combined with literature. The herb-component-target network and ingredient-target-disease interaction Protein-protein interaction (PPI) network of PXZOL were constructed by Cytoscape 3.6.0 software. A core target network was constructed by screening targets in the PPI network. Gene Ontology (GO) analysis and Pathway analysis of the core target network were performed by using the ClueGO plugin. Organ localization of core targets was detected using the BioGPS database. Results GO analysis showed that PXZOL exerted antitussive effect mainly by regulating nuclear transcription factor-κB (NF-κB) signaling. The role of depletion is mainly achieved by the synthesis and regulation of related proteins. Pathway results showed that PXZOL exerts antitussive effects mainly through mitogen-activated protein kinase (MAPK) signaling pathway, retinoic acid-inducible gene-I (RIG-I)-like receptor signaling pathway, interleukin 17 (IL-17) signaling pathway, and TNF receptor associated factor 6 (TRAF6)-mediated NF-κB activation. The role of elimination is mainly achieved through a variety of immune and inflammatory signaling pathways. In terms of organ localization, nearly 50% of target sites for antitussive targets, targets for elimination, and common targets have more expression in the lungs and large intestine. Conclusion PXZOL is based on the theory of traditional Chinese medicine "lung and large intestine phase" and the prescription of latent medicine, modern pharmacology research showed that the effect of "resolving accumulation and relieving cough" mostly concentrated on immunity and inflammation, and network pharmacology research found that the target and its common target have nearly 50% more expression in the lungs and large intestine. From the infective disease and the network of action, we suggest that the efficacy of PXZOL is manifested by mucosal immunity and inflammation-mediated pathways. The scientific nature of the theory with the large intestine also lays the foundation for further in-depth research and verification of the model and clinical practice of pediatric food accumulation cough.

R285.5

国家重大新药创制重大专项：中药复方药理学研究与药效评价关键技术（2009ZX09502-015）；山东省自主创新和成果转化课题（2014ZZCX02104）；泰山学者工程专项经费项目（ts201511107）