基于网络药理学、分子对接及实验验证探讨五苓散联合桃红四物汤抗心力衰竭的作用机制  

Exploration on mechanism of Wuling Powder combined with Taohong Siwu Decoction in treatment ofheart failure based on network pharmacology,molecular docking,and experimental validation

作　　者：吴平[1] 施佳晨 吴三兵[3] 王忆勤 WU Ping;SHI Jiachen;WU Sanbing;WANG Yiqin(Shanghai University of Traditional Chinese Medicine,Shanghai 201203,China;Longhua Hospital,Shanghai University of Traditional Chinese Medicine,Shanghai 200032,China;The Second Affiliated Hospital of Anhui University of Chinese Medicine,Hefei 230061,Anhui,China;Shanghai Key Laboratory of Health Identification and Assessment,Shanghai 201203,China)

机构地区：[1]上海中医药大学,上海201203 [2]上海中医药大学附属龙华医院,上海200032 [3]安徽中医药大学第二附属医院,安徽合肥230061 [4]上海市健康辨识与评估重点实验室,上海201203

出　　处：《上海中医药大学学报》2023年第3期63-73,共11页Academic Journal of Shanghai University of Traditional Chinese Medicine

基　　金：上海市科技计划资助项目(21DZ2271000)。

摘　　要：目的通过网络药理学、分子对接及实验验证探究五苓散和桃红四物汤合用治疗心力衰竭(心衰)的作用机制。方法通过检索化合物及疾病相关数据库进行网络药理学预测,运用Cytoscape软件进行可视化,DAVID网站进行基因本体(GO)富集分析和京都基因和基因组百科全书(KEGG)通路预测,对筛选获得的核心基因与活性成分进行分子对接,预测其结合程度。通过阿霉素诱导H9C2心肌细胞损伤模型,采用两方合方或五苓散单方干预,通过CCK-8和Western blot试验验证合方及单方的抗炎效果。结果①网络药理学分析发现,合方与心衰共有205个共同基因、67个活性较高的化合物,预测其相关信号通路可能为Toll样受体(TLR)通路。②TLR4基因和主要化合物进行分子对接,其能量<-5 kcal/mol。③CCK-8实验结果表明,合方比五苓散单方对H9C2细胞活力有更好的增强作用(P<0.001)。④Western blot实验结果表明,合方比五苓散单方对TLR通路蛋白TLR4、髓样分化因子(MyD88)的表达有更强的抑制作用(P<0.05)。结论五苓散和桃红四物汤合用可以较好地抗心肌细胞损伤,且其效果优于五苓散单方,而TLR4信号通路在其中起了重要作用。Objective:To explore the mechanism of Wuling Powder combined with Taohong Siwu Decoction in the treatment of heart failure through network pharmacology,molecular docking and experimental verification.Methods Compound and disease-related databases were searched for network pharmacology predictions.Cytoscape software was used for visualization,DAVID website was used for Gene Ontology(GO)enrichment analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway prediction,and molecular docking was performed for core genes of interest to predict their binding degree.The doxorubicin induced H9C2 myocardial cell injury model was used to verify the anti-inflammatory effects of the combination of two formulas(combined formula)and Wuling Powder single formula.Results①Network pharmacological analysis showed that there were 205 common genes and 67 compounds with higher activity between combined formula and heart failure,and the predicted related signaling pathway may be Toll-like receptor(TLR)pathway.②Molecular docking was carried out between TLR4 gene and major compounds,and the energy was<-5 kcal/mol.③CCK-8 experiment results showed that the combined formula had a better enhancing effect on H9C2 cell vitality than Wu Ling Powder single formula(P<0.001).④Western blot experiment results showed that the combined formula had a stronger inhibitory effect on the expression of TLR4 and myeloid differentiation primary-response protein 88(MyD88)proteins in TLR pathway compared with Wu Ling Powder single formula(P<0.05).Conclusion The combination of Wu Ling Powder and Taohong Siwu Decoction can effectively resist myocardial cell damage,and its effect is better than that of Wu Ling Powder single formula,and TLR4 signaling pathway plays an important role in it.

关 键 词：五苓散 桃红四物汤 心力衰竭 网络药理学 分子对接 体外细胞实验 

分 类 号：R285[医药卫生—中药学]