中医药信息2025，Vol.42Issue(3)：27-36,10.DOI:10.19656/j.cnki.1002-2406.20250306
基于网络药理学和实验验证探讨血府逐瘀汤治疗脑梗死的作用机制
Exploration of the Mechanism of Xuefu Zhuyu Decoction in the Treatment of Cerebral Infarction Based on Network Pharmacology and Experimental Verification
摘要
Abstract
Objective:To explore the mechanism of Xuefu Zhuyu Decoction(XFZY)in the treatment of cerebral infarction based on network pharmacology and animal experimental verification.Methods:Based on network pharmacology,multiple databases were used to obtain the drug components and their corresponding target genes,as well as the disease targets related to cerebral infarction.The intersection of drug targets and disease targets was taken,and the"drug-component-intersection targets"network diagram was constructed.Protein-protein interaction(PPI)network of drug-disease intersection targets was drawn to screen for core targets.Gene Ontology(GO)functional enrichment analysis and KEGG pathway enrichment analysis were performed.The key targets were molecularly docked with the major components,and the docking results with low binding energy were visualized.Thirty male SD rats were randomly divided into the sham operation group,model group,positive drug group(28 mg/kg of Ginnan),XFZY low-dose group(0.9 g/kg),and XFZY high-dose group(3.6 g/kg),with 6 rats in each group.Except for the sham operation group,the middle cerebral artery occlusion model was prepared by Longa's method.The rats in the sham operation and model groups were gavaged with physiological saline,while the other groups were treated with corresponding drugs once daily for 72 hours.After 72 hours,brain tissue was collected for transmission electron microscopy(TEM)to observe ultrastructural changes,and serum TNF-α and SOD levels were detected by ELISA.Western blot and qRT-PCR were used to detect the expression of key target proteins and mRNAs,which preliminarily validated the network pharmacology results.Results:Using network pharmacology,key targets such as STAT3,AKT1,EGFR,PIK3CA,and MAPK3 were identified.The enriched key pathways included AGE/RAGE,PI3K/Akt,HIF-1,RAS,Ca2+,and MAPK.Molecular docking results showed that the major active components of XFZY had good binding affinity with STAT3,Bax,Bcl-2,and EGFR.TEM results revealed that XFZY could reduce cell edema and decrease brain tissue structural damage.ELISA results indicated that XFZY significantly reduced serum TNF-α levels and increased SOD levels in cerebral infarction rats.Furthermore,XFZY significantly reduced the expression of Bax and the p-STAT3/STAT3 ratio in brain tissue,while significantly increasing the expression of Bcl-2,LC3Ⅱ protein,and VEGF mRNA.Conclusion:Xuefu Zhuyu Decoction may act on core targets such as STAT3,Bax,and VEGF,inhibiting the activation of the STAT3 pathway,reducing oxidative stress and inflammation,and regulating apoptosis and autophagy.This helps to repair nerve cells,thereby exerting anti-cerebral infarction effects.关键词
血府逐瘀汤/脑梗死/网络药理学/分子对接/凋亡/炎症Key words
Xuefu Zhuyu Decoction/Cerebral infarction/Network pharmacology/Molecular docking/Apoptosis/Inflammation引用本文复制引用
王思齐,陈振振..基于网络药理学和实验验证探讨血府逐瘀汤治疗脑梗死的作用机制[J].中医药信息,2025,42(3):27-36,10.基金项目
首都医科大学学生科研创新项目(XSKY2024181) （XSKY2024181）
