【摘要】 目的 基于网络药理学验证丹参酮IIA(Tan-IIA)治疗脓毒症的分子机制。方法 在Pubchem和Swiss Target Prediction上搜索丹参酮IIA的结构和相应的蛋白质靶点，利用Cytoscape＿v3.10.0构建化合物靶点网络。在DisGeNET和GeneCardsSuite数据库中搜索脓毒症靶点。得到复合靶点与疾病靶点的交集靶点，并将重合靶点导入STRING数据库，构建PPI网络，进而对靶点进行GO和KEGG富集分析。培养及转染RAW 264.7细胞，通过蛋白质免疫印记(Western blot)检测相关信号通路中关键蛋白的磷酸化程度。结果 在PPI网络中，Tan-IIA可能主要通过雄激素受体(AR)、非受体型蛋白酪氨酸磷酸酶11(PTPN11)、蛋白酪氨酸磷酸酶受体C(PTPRC)等关键靶点干预脓毒症。GO和KEGG分析显示，Tan-IIA对脓毒症的治疗主要涉及蛋白酪氨酸磷酸酶活性等生物学过程。信号通路主要包括MAPK级联通路、T细胞受体信号通路。在细胞水平上加以验证，Tan-IIA可以显著抑制含SH2结构域的蛋白酪氨酸磷酸酶-2(SHP2)的表达，抑制丝裂原活化蛋白激酶(MAPK)级联通路。结论 本研究以网络药理学为基础，在细胞水平上进一步验证，表明Tan-IIA可以通过抑制MAPK级联通路，发挥对脓毒症的治疗作用，为后续基础研究提供参考。更多还原

【Abstract】 Objective To validate the molecular mechanism of tanshinone IIA(Tan-IIA) in the treatment of sepsis based on network pharmacology.Methods The main components of Tan-IIA and their corresponding protein targets were searched on PubChem and Swiss Target Prediction. The compound-target network was constructed using Cytoscape＿v3.10.0. Sepsis-related targets were retrieved from the DisGeNET and GeneCards Suite databases. The intersection of compound targets and disease targets was identified, and the overlapping targets were imported into the STRING database to construct a protein-protein interaction(PPI) network. Further GO and KEGG enrichment analyses were performed on the targets. RAW 264.7 cells were cultured and transfected, and the phosphorylation levels of key proteins in related signaling pathways were detected by Western blot.Results In the PPI network, Tan-IIA primarily acted on sepsis through key targets such as the androgen receptor(AR), non-receptor type protein tyrosine phosphatase 11(PTPN11), and protein tyrosine phosphatase receptor type C(PTPRC). GO and KEGG analyses revealed that the therapeutic effects of Tan-IIA on sepsis mainly involved biological processes such as protein tyrosine phosphatase activity. The signaling pathways primarily included the MAPK cascade pathway and the T-cell receptor signaling pathway. Cellular-level validation showed that Tan-IIA significantly inhibited the expression of Src homology 2 domain-containing protein tyrosine phosphatase-2(SHP2) and suppressed the MAPK cascade pathway.Conclusion Based on network pharmacology and further cellular-level validation, this study demonstrated that Tan-IIA exerts therapeutic effects on sepsis by inhibiting the MAPK cascade pathway, providing a reference for subsequent basic research.更多还原