基于网络药理学和高通量测序探析丹参酮ⅡA治疗慢性心力衰竭的分子机制OA

Objective:To explore the mechanism of tanshinone ⅡA in the treatment of chronic heart failure(CHF)through network pharmacology,molecular docking,and high-throughput sequencing datasets.Methods:The SMILES notation and 2D structure of tanshinone ⅡA were retrieved from the PubChem database and imported into SwissTarget Prediction,PharmMapper,and SuperPred databases to screen compound-related targets.CHF-associated disease targets were collected from the GeneCards and OMIM databases,and intersecting targets were identified.A protein-protein interaction(PPI)network was constructed using the STRING database,and hub genes were screened via Cytoscape.GO functional and KEGG pathway enrichment analyses were performed on the DAVID platform.Molecular docking between tanshinone ⅡA and proteins encoded by hub genes was conducted using AutoDock software.Finally,core genes and enriched pathways were validated using the GSE185631 high-throughput sequencing dataset from the GEO database.Results:A total of 443 candidate targets for tanshinone ⅡA and 3312 CHF-related disease targets were screened,yielding 221 intersecting targets.Ten core hub genes,including CASP3,EGFR,and MAPK1,were identified via Cytoscape.KEGG enrichment analysis revealed that the intersecting targets were significantly enriched in key signaling pathways such as PI3K-Akt,MAPK,and EGFR.Molecular docking results showed that the binding energies between tanshinone ⅡA and all 10 hub proteins were lower than-5.0 kcal/mol,with the lowest binding energy observed for MAPK1(-9.0 kcal/mol),indicating stable hydrogen bond interactions.Validation using the GSE185631 dataset demonstrated that the expression levels of EGFR,MAPK1,and NF-κB were significantly upregulated in the CHF model group(P<0.01)and showed marked differences after intervention(P<0.05).The enriched pathways of differentially expressed genes were highly consistent with the predicted results.Conclusion:Tanshinone ⅡA exerts therapeutic effects on CHF by coordinately regulating core pathological processes including myocardial fibrosis,oxidative stress,and inflammatory responses through multi-target and multi-pathway mechanisms.EGFR,MAPK1,and NF-κB were identified as its key regulatory targets,providing reliable experimental evidence for the application of tanshinone ⅡA in CHF treatment.