疏木培土方基于多条炎症通路多靶点治疗桥本甲状腺炎的药理机制探究

Exploration of the Pharmacological Mechanism of Shumu Peitu Formula in Treating of Hashimoto’s Thyroiditis Based on Multiple Inflammatory Pathways

摘要: 目的：本研究采用网络药理学方法，探究疏木培土方治疗桥本甲状腺炎(Hashimoto’s thyroiditis, HT)的潜在物质基础与作用机制。方法：通过TCMSP (https://old.tcmsp-e.com/)数据库筛选复方活性成分并筛选其作用靶点，经Cytoscape3.10.4构建“成分–靶点”网络，以“度值(Degree)”为指标识别关键活性成分；在Genecards (https://www.genecards.org/)、OMIM (https://www.omim.org/)数据库获取的HT相关靶点，将药物预测靶点与疾病靶点通过微生信平台(https://www.bioinformatics.com.cn/)取交集，得到靶点，并在Metascape平台(https://metascape.org)以“Homosapiens”进行基因本体(GO)功能富集分析和京都基因与基因组百科全书(KEGG)通路富集分析；通过STRING12.0 (https://cn.string-db.org/)数据库构建共同靶点PPI网络，通过Cytoscape中的MCODE插件筛选核心模块，再经cytoHubba插件筛选得到核心靶点；将筛选获得的核心靶点与关键活性成分进行分子对接验证。结果：经筛选获得152个共同靶点，如JUN、CASP3、IL6等，确定木犀草素(Luteolin)、山奈酚(Kaempferol)、槲皮素(Quercetin)等关键活性成分；GO与KEGG富集分析显示，疏木培土方–桥本甲状腺炎共同靶点显著富集于自身免疫性甲状腺疾病等免疫炎症相关通路。分子对接验证表明核心成分与核心靶点结合活性良好。结论：疏木培土方可能通过多成分、多靶点、多通路协同发挥免疫调节与抗炎作用，为其治疗HT的科学内涵提供了潜在的作用机制假说和进一步实验研究的方向。

Abstract: Objective: This study employed a network pharmacology approach to investigate the potential material basis and mechanism of action of the Shumu Peitu formula in the treatment of Hashimoto’s thyroiditis (HT). Methods: The active components of the compound formula and their corresponding targets were screened via the TCMSP database (https://old.tcmsp-e.com/). A “component-target” network was constructed using Cytoscape 3.10.4, and key active components were identified based on the “Degree” value. HT-related targets were obtained from the Genecards (https://www.genecards.org/) and OMIM (https://www.omim.org/) databases. The intersection of the drug-predicted targets and disease targets was obtained using the MicroBioinformatics platform (https://www.bioinformatics.com.cn/). Gene Ontology (GO) functional enrichment analysis and Kyoto Encyclopedia of Genes and Genomes (KEGG) pathway enrichment analysis were performed on the intersecting targets in the Metascape platform (https://metascape.org) with the organism set as Homo sapiens. A protein-protein interaction (PPI) network of the common targets was constructed via the STRING 12.0 database (https://cn.string-db.org/). Core modules were screened using the MCODE plugin in Cytoscape, and core targets were further identified with the cytoHubba plugin. Molecular docking verification was conducted between the screened core components and core targets. Results: A total of 152 common targets were identified, including JUN, CASP3, and IL6. Key active components such as Luteolin, Kaempferol, and Quercetin were confirmed. GO and KEGG enrichment analyses revealed that the common targets of the Shumu Peitu formula and HT were significantly enriched in immune-inflammatory related pathways, such as autoimmune thyroid disease. Molecular docking verification demonstrated favorable binding activity between the core components and core targets. Conclusion: The Shumu Peitu formula may exert immunomodulatory and anti-inflammatory effects through the synergistic action of multiple components, multiple targets, and multiple pathways, providing a scientific basis for its therapeutic efficacy in treating HT.