目的 基于网络药理学与分子对接技术，预测桔梗汤干预慢性咽炎的关键靶点及作用通路，并通过动物实验验证预测结果。方法 建立乙型溶血性链球菌诱导的慢性咽炎大鼠模型，探究桔梗汤对慢性咽炎大鼠血清炎症因子及咽部组织病理变化的影响。使用人类在线孟德尔遗传数据库（Online Mendelian Inheritance in Man， OMIM）、DrugBank 和 GeneCards 数据库筛选慢性咽炎关键靶点；UHPLC-QE-MS 分析桔梗汤化学成分，结合中药系统药理学数据库与分析平台（Traditional Chinese Medicine Database and Analysis Platform，TCMSP）和SwisstargetPredicition 数据库确认成分作用靶点。使用 STRING 平台构建关键靶点蛋白互作网络；通过注释、可视化和综合发现数据库（Database for Annotation，Visualization and Integrated Discovery，DAVID）对关键靶点进行基因本体（Gene Ontology，GO）分析和基因组百科全书（Kyoto Encyclopedia of Genes and Genomes，KEGG）信号通路富集分析；通过 AutoDock Tools 1.5.6 软件对有效成分及核心靶点进行分子对接；Western Blot 法验证预测结果。结果 体内实验显示，桔梗汤可有效降低慢性咽炎大鼠血清中 IL-1β、IL-6、TNF-α、ICAM-1、MCP1 水平（P＜0.05），并逆转咽部组织病理损伤。得到 94 个桔梗汤主要活性成分，协同作用于 311 个靶点，参与外源性刺激反应、药物反应、蛋白酪氨酸激酶活性等生物学过程，调控 PI3K/AKT、MAPK、Ras 等信号通路；分子对接结果显示关键靶点与有效成分间均有较强的结合能力；Western Blot 显示桔梗汤可显著降低 TLR4蛋白表达及 P38 MAPK 磷酸化水平。结论 桔梗汤通过调控 TLR4/P38 MAPK 信号通路降低血清炎症因子及逆转咽部组织病理变化从而治疗慢性咽炎。

Objective To elucidate the key targets and the mechanism of Jiegeng Decoction in treating chronic pharyngitis through an integrated approach of network pharmacology and molecular docking，and to verify the predicted results through animal experiments. Methods A rat model of chronic pharyngitis was induced by β –hemolytic streptococcus to assess the impact of Jiegeng Decoction on serum inflammatory factors and the pathological alterations in pharyngeal tissues. Key targets associated with chronic pharyngitis were identified through databases such as OMIM，DrugBank， and GeneCards. The chemical constituents of Jiegeng Decoction were characterized by UHPLC-QE-MS coupled to the TCMSP and swisstarget Predicition databases. Subsequently，STRING database was applied to construct protein-protein interaction network of key targets， and the Database for Annotation， Visualization and Integrated Discovery （DAVID） was utilized to perform Gene Ontology （GO） function and Kyoto Encyclopedia of Genes and Genomes （KEGG） pathway enrichment analysis. Furthermore，molecular docking of the active components with the core targets was performed by using AutoDock Tools1.5.6. Western Blot was carried out to verify prediction results. Results In vivo studies revealed that Jiegeng Decoction significantly decreased the serum levels of IL-1β，IL-6，TNF- α，ICAM-1，and MCP-1 in rats with chronic pharyngitis （P＜0.05），and ameliorated the pathological damage in pharyngeal tissues. A total of 94 principal bioactive components were obtained， which acted synergistically on 311 targets，participated in responses to exogenous stimuli，drug metabolism，and protein tyrosine kinase activities，and played a significant regulatory role in the PI3K/AKT，MAPK，and Ras signaling pathways. The results of molecular docking showed that there was a strong binding ability between the key targets and the active ingredients. Western Blot analysis indicated that Jiegeng Decoction notably reduced the expression of the TLR4 protein and the phosphorylation level of P38 MAPK. Conclusion Jiegeng Decoction exerts its therapeutic effect on chronic pharyngitis by modulating the TLR4/P38 MAPK signaling pathway，attenuating serum inflammatory factors，and reversing the pathological changes in pharyngeal tissues.

R285.5

大学生创新创业训练计划项目（S202410680024）；云南省科技人才和平台计划项目（202105AG070012）