The potential mechanism of atorvastatin in the treatment of chronic subdural hematoma based on network pharmacology and experimental validation
- VernacularTitle:基于网络药理学和实验验证研究阿托伐他汀治疗慢性硬膜下血肿的潜在机制
- Author:
Taoning WANG
1
;
Changwang DU
;
Ruichun LI
;
Chen LIANG
Author Information
- Publication Type:Journal Article
- Keywords: atorvastatin; chronic subdural hematoma(CSDH); network pharmacology; molecular docking; inflammatory factor
- From: Journal of Xi'an Jiaotong University(Medical Sciences) 2025;46(4):633-640
- CountryChina
- Language:Chinese
- Abstract: Objective To investigate the potential mechanism of atorvastatin in treating chronic subdural hematoma(CSDH)through network pharmacology and experimental validation,thereby providing theoretical foundation and experimental evidence for further basic and clinical research.Methods The target genes of atorvastatin and CSDH-related genes were identified through network databases including chEMBL,NCBI PubChem Compound,SwissTargetPrediction,GeneCards,and DisGeNET.Potential target genes of atorvastatin for CSDH treatment were screened using Venn diagrams,followed by enrichment analysis performed with R software.Protein-protein interaction(PPI)analysis was conducted using the STRING database,and molecular docking was employed to verify the binding capability between atorvastatin and the proteins encoded by the target genes.An endothelial cell inflammation model was established to assess the effects of atorvastatin on the expression and secretion of inflammation-related genes using Real-time quantitative reverse transcription polymerase chain reaction(RT-qPCR)and enzyme-linked immunosorbent assay(ELISA).The impact of atorvastatin on endothelial barrier function in the inflammation model was evaluated using the FITC-Dextran permeability assay.Results A total of 19 potential target genes of atorvastatin for CSDH treatment were identified.Enrichment analysis indicated that these genes are primarily involved in the regulation of inflammation,angiogenesis,and coagulation/fibrinolysis processes.Based on the PPI analysis,five key target genes-matrix metalloproteinase 2(MMP-2),matrix metalloproteinase 9(MMP-9),interleukin-6(IL-6),C-X-C motif chemokine ligand 8/interleukin 8(CXCL-8/IL-8),and serpin family E member 1(SERPINE-1)—were selected for molecular docking,which revealed favorable binding interactions between atorvastatin and these proteins.In the endothelial cell inflammation model,atorvastatin suppressed the expression and secretion of the aforementioned genes as well as inflammatory markers such as intercellular adhesion molecule 1(ICAM-1)and vascular cell adhesion molecule 1(VCAM-1)(IL-6:F=64.526,P＜0.001;CXCL-8/IL-8:F=37.779,P＜0.001;ICAM-1:F=86.253,P＜0.001;VCAM-1:F=39.631,P＜0.001;MMP-2:F=264.413,P＜0.001;MMP-9:F=86.675,P＜0.001;SERPINE-1:F=71.180,P＜0.001).Furthermore,atorvastatin alleviated endothelial barrier dysfunction caused by inflammation(F=343.890,P＜0.001).Conclusion Atorvastatin may exert therapeutic effects on CSDH by inhibiting inflammatory responses.
