目的 基于网络药理学、分子对接和体内实验方法探讨感冒清热片抗肺损伤的作用机制。方法 以中药 系统药理学数据库和分析平台（TCM-SP）、Genecards 等数据库，筛选感冒清热片治疗肺损伤的潜在作用靶点。 采用 Cytoscape 3.9.0 软件构建“中药-有效成分-靶点”网络，并用生物信息云平台对潜在作用靶点进行基因本 体（GO）功能与京都基因和基因组百科全书（KEGG）通路富集分析。建立蛋白互作（PPI）网络，并与“中药-有效 成分-靶点”网络进行交集分析，筛选关键靶蛋白。将关键靶蛋白和有效成分进行分子对接。建立肺损伤小鼠 模型验证感冒清热片对关键靶标蛋白的作用。结果 共筛选出感冒清热片治疗肺损伤的作用靶点 707 个，对应 11 味中药中 107 种化合物。利用构建的“中药-有效成分-靶点”网络发现感冒清热片可能通过豆甾醇、芦丁、 金合欢素等有效成分对前列腺素 G/H 合成酶 1（PTGS1）、雄激素受体（AR）、乙酰胆碱酯酶（ACHE）等作用靶点 进行调控。利用 PPI 网络发现 SRC 酪氨酸激酶（SRC）、表皮生长因子受体（EGFR）、信号转导因子和转录激活 因子 3 （STAT3） 等核心靶点。通过 PPI 网络与“中药-有效成分-靶点”网络交集分析，筛选出关键靶标蛋白 周期蛋白依赖性激酶 1（CDK1）、CDK2、EGFR、雌激素受体 1（ESR1）和 SRC。分子对接研究显示，感冒清热 片中的豆甾醇、芦丁、金合欢素分别与 CDK1、CDK2、EGFR、ESR1、SRC 有较好的结合能力。体内实验发现 感冒清热片可剂量依赖性地减轻肺损伤小鼠的肺组织损伤、炎性浸润，降低 TNF-α、IL-1β、IL-6 的含量，增 强 CDK1、CDK2 的表达，降低 EGFR、ESR1 和 SRC 的表达。结论 感冒清热片对肺损伤的治疗作用可能通过 其所含的豆甾醇、芦丁、金合欢素等关键活性成分，作用于 CDK1、CDK2、EGFR、ESR1、SRC 等关键靶标蛋 白，调控神经活性配体-受体相互作用、癌症途径、钙信号通路等关键信号通路来实现的。

Objective To investigate the mechanism of Ganmao Qingre Pills （GQP） against lung injury based on network pharmacology，molecular docking and in vivo experiments. Methods The potential targets of GQP in the treatment of lung injury were screened through traditional Chinese medicine systems pharmacology database and analysis platform （TCM-SP） and Genecards. A “Chinese medicine-active ingredients-targets” network was constructed using Cytoscape 3.9.0 software，then gene ontology （GO） function and Kyoto encyclopaedia of genes and genomes （KEGG） pathway enrichment analysis for potential targets were conducted using a bioinformatics cloud platform. We established a protein-protein interaction （PPI） network，which was intersected with “Chinese medicine-active ingredients-targets” network to obtain core targets. The molecular docking between key target proteins and active ingredients was performed. The effect of GQP on these key target proteins was verified by using a mouse model of lung injury. Results A total of 707 targets for the treatment of lung injury by GQP were identified， corresponding to 107 active ingredients in 11 Chinese medicines. It was found that GQP might regulate targets such as PTGS1， AR， and ACHE through active ingredients including stigmasterol， luteolin， and acacetin using the "Chinese medicine-active ingredients-targets" network analysis. Core targets such as SRC，EGFR，and STAT3 were discovered by using the PPI network. Key target proteins，including CDK1，CDK2，EGFR，ESR1 and SRC，were screened through the intersection analysis of the PPI network and “Chinese medicine-active ingredients-targets” network. Molecular docking study showed that stigmasterol， luteolin and acacetin had good binding effects with CDK1，CDK2，EGFR，ESR1，and SRC，respectively. In vivo experiments revealed that GQP dose-dependently attenuated lung injury and inflammatory infiltration，reduced the release of pro-inflammatory factors TNF-α，IL-1β and IL-6，increased the expression of CDK1 and CDK2，and decreased the expression of EGFR，ESR1 and SRC in lung injury mice. Conclusion The therapeutic effect of GQP against lung injury may be achieved through interaction of key active ingredients （stigmasterol， luteolin， and acacetin） and key target proteins （CDK1， CDK2， EGFR， ESR1， SRC）， and regulation of key signaling pathways such as neuroactive ligand-receptor interactions，cancer pathways，and calcium signaling pathways.

R285.5

广东省中医药局课题（20222009）