中国中医药信息杂志2024，Vol.31Issue(5)：28-35,8.DOI:10.19879/j.cnki.1005-5304.202306297
基于网络药理学与动物实验验证探究防己茯苓汤治疗心肌纤维化作用机制
Exploration on the Mechanism of Fangji Fuling Decoction in Treatment of Myocardial Fibrosis Based on Network Pharmacology and Animal Experimental Verification
摘要
Abstract
Objective To investigate the potential targets and relevant mechanism of Fangji Fuling Decoction in the treatment of myocardial fibrosis(MF)based on network pharmacology;To verify them through animal experiments.Methods TCMSP was used to retrieve and screen the active components and related targets of Fangji Fuling decoction;MF disease targets were retrieved through GeneCards,OMIM,and DisGeNET databases,and the intersection of the two was obtained to obtain potential therapeutic targets of Fangji Fuling Decoction for MF.STRING database and Cytoscape 3.7.2 software were used to establish protein-protein interaction network for the treatment of MF to screen core targets.GO analysis and KEGG pathway enrichment analysis were performed on core targets using the DAVID database.The MF model mice was established by subcutaneous injection of isoproterenol,and intervened by Fangji Fuling Decoction for 14 d.Myocardial injury and collagen deposition were observed by histopathology.The CK-MB,TNF-α,IL-1β,IL-6 and IL-10 contents in serum were detected by ELISA.The mRNA and protein expression of PI3K/Akt/p65 pathway in myocardial tissue were detected by RT-qPCR and immunohistochemistry staining.Myocardial ultrastructure was observed by transmission electron microscope.Results Totally 127 active components and 200 targets for MF were selected from Fangji Fuling Decoction.Kanzonol F,glycyrrhizin O,and glabridin were the main active components,PIK3CA,AKT1,and EP300 were the main core targets.The PI3K-Akt signaling pathway,apoptosis pathway,FoxO signaling pathway,mTOR signaling pathway,cell aging pathway,and TGF-β signal pathways were closely related to MF.Compared with the model group,the heart weight index,heart to tibia ratio,and myocardial cell cross-sectional area of mice were significantly reduced in the Fangji Fuling Decoction group(P<0.001);the serum CK-MB content significantly decreased(P<0.01),the contents of pro-inflammatory cytokine TNF-α,IL-1β and IL-6 were significantly reduced(P<0.01,P<0.05),and the anti-inflammatory cytokine IL-10 content significantly increased(P<0.05);inflammatory cell infiltration,myocardial injury,collagen deposition,and fibrosis degree were significantly reduced;RT-qPCR and immunohistochemistry staining showed that Fangji Fuling Decoction significantly reduced the mRNA and protein expression levels of PI3K/Akt/p65 pathway in myocardial tissue(P<0.05,P<0.001);transmission electron microscopy showed that Fangji Fuling Decoction could improve the ultrastructure of myocardial tissue,especially the mitochondrial structure.Conclusion Fangji Fuling Decoction acts on targets such as PIK3CA and AKT1 through active components such as Kanzonol F,glycyrrhizic acid O,and light glycyrrhizin,regulating the PI3K/Akt/p65 signaling pathway and exerting anti MF effects.关键词
防己茯苓汤/心肌纤维化/网络药理学/PI3K/Akt/p65信号通路/小鼠Key words
Fangji Fuling Decoction/myocardial fibrosis/network pharmacology/PI3K/Akt/p65 signaling pathway/mice分类
医药卫生引用本文复制引用
石立鹏,邓静薇,杜旭勤,尹二谦,陈欣..基于网络药理学与动物实验验证探究防己茯苓汤治疗心肌纤维化作用机制[J].中国中医药信息杂志,2024,31(5):28-35,8.基金项目
中国博士后科学基金面上资助"地区专项支持计划"(2023MD744148) （2023MD744148）
重庆市自然科学基金(cstc2021jcyj-bshX0215) （cstc2021jcyj-bshX0215）
重庆市教委科学技术研究项目(KJQN202315105) （KJQN202315105）
重庆医科大学中医药学院杏林计划项目(2021-ZDXK-DB03) （2021-ZDXK-DB03）
