基于网络药理学和分子对接技术探讨红景天苷在脓毒症相关急性肺损伤中的机制研究

Network Pharmacology and Molecular Docking-Based Mechanistic Investigation of Salidroside in Sepsis Induced Acute Lung Injury

摘要: 目的：通过网络药理学和分子对接技术，分析红景天苷(Salidroside, SDS)治疗脓毒症相关急性肺损伤(acute lung injury, ALI)的潜在靶点和作用机制。方法：通过TCMSP、SwissTarget、CTD、PharmMapper、ETCM及GeneCards数据库筛选SDS相关靶点，在GeneCards与OMIM数据库获取ALI相关疾病靶点，利用R软件获得交集靶点。采用STRING数据库构建蛋白互作网络(PPI)，并结合拓扑分析筛选关键靶点。进一步利用R软件对交集靶点进行GO功能富集分析及KEGG通路富集分析。采用分子对接技术评估SDS与核心靶点SRC的结合能力。结果：共获得SDS潜在作用靶点250个，ALI相关基因12,184个，二者交集靶点234个。PPI网络分析显示，核心靶点主要包括TNF、BCL2、SRC、IL6及IL1B等。GO富集分析提示交集靶点主要参与氧化应激反应、细胞应激反应及凋亡调控等生物过程，并涉及蛋白激酶活性及细胞因子相关分子功能。KEGG分析显示，靶点主要富集于PI3K-Akt、MAPK、NF-κB、TNF及IL-17等炎症相关信号通路，并与HIF-1及凋亡通路密切相关。分子对接结果表明，SDS与SRC具有较强结合活性(−7.6 kcal/mol)。结论：SDS可能通过多靶点、多通路协同调控发挥对ALI的干预作用，其中SRC可能为关键靶点之一。本研究为SDS治疗ALI的机制研究提供理论依据。

Abstract: Objective: To investigate the potential targets and molecular mechanisms of salidroside (SDS) in the treatment of acute lung injury (ALI) using network pharmacology and molecular docking approaches. Methods: SDS-related targets were retrieved from TCMSP, SwissTarget, CTD, PharmMapper, ETCM, and GeneCards databases. ALI-related disease targets were obtained from GeneCards and OMIM databases. The intersection targets were identified using the R software. A protein-protein interaction (PPI) network was constructed using the STRING database, and key targets were screened through topological analysis. GO functional enrichment analysis and KEGG pathway enrichment analysis were further performed using R software. Molecular docking was employed to evaluate the binding affinity between SDS and the core target SRC. Results: A total of 250 potential targets of SDS and 12,184 ALI-related genes were identified, with 234 overlapping targets. PPI network analysis indicated that the core targets mainly included TNF, BCL2, SRC, IL6 and IL1B. GO enrichment analysis indicated that the intersecting targets were mainly involved in oxidative stress response, cellular stress response, and regulation of apoptotic processes, and were associated with molecular functions, such as protein kinase activity and cytokine-related binding. KEGG pathway analysis showed that these targets were primarily enriched in PI3K-Akt, MAPK, NF-κB, TNF, and IL-17 signaling pathways, as well as the HIF-1 signaling and apoptosis-related pathways. Molecular docking results demonstrated that SDS exhibited strong binding affinity with SRC, with a binding energy of −7.6 kcal/mol. Conclusion: SDS may exert therapeutic effects on ALI through multi-target and multi-pathway synergistic regulation, with SRC potentially serving as a key target. This study provides a theoretical basis for further investigation of the molecular mechanisms of SDS in ALI.