基于系统药理学和分子对接探讨浙贝母-瓜蒌配伍调控慢性阻塞性肺病并发心脏衰竭的作用机制  

The mechanism of Fritillariae Thunbergii Bulbus-Trichosanthis Fructu pairing in regulating heart failure complicated by chronic obstructive pulmonary disease based on systems pharmacology and molecular docking

作　　者：方孟香 程成[2] 曹铭晨 任炜 杨智威[2] 李文静[2] 辛晓玮[2] 刘月芬[2] 徐龙[2] FANG Mengxiang;CHENG Cheng;CAO Mingchen;REN Wei;YANG Zhiwei;LI Wenjing;XIN Xiaowei;LIU Yuefen;XU Long(The Second Traditional Chinese Medicine Hospital of Qingdao West Coast New District,Qingdao 266427,China;The Affiliated Hospital of Qingdao University,Qingdao 266300,China)

机构地区：[1]青岛市西海岸新区第二中医医院,山东青岛266427 [2]青岛大学附属医院,山东青岛266300

出　　处：《山东科学》2024年第4期45-55,共11页Shandong Science

基　　金：2022年青岛市中医药科技项目(2022-zyyq08);2023年山东省中医药科技发展项目(Q-2023204);山东省自然科学基金面上项目(ZR2022MH069);2023年山东省医药卫生科技项目(202302021683)。

摘　　要：基于GEO数据库挖掘慢性阻塞性肺疾病(COPD)和心力衰竭(HF)关联靶点,检索浙贝母、瓜蒌化学成分及靶点,以获得其调控COPD并发HF潜在靶点,挖掘靶点功能及通路注释分析,构建组织特异性蛋白相互作用(PPI)网络。浙贝母-瓜蒌影响COPD并发HF进展共涉及靶点227个,包括表达上调基因153个,表达下调基因74个;网络拓扑学分析显示PPI网络平均介数为0.4,平均度值为1.83,关键靶点包括RPS23、SNU13、NOL6、ELAVL1、NCL等;细胞组分定位于内膜系统、核内体和细胞外囊泡;生物学过程涉及囊泡介导的运输、基于微管的运动、细胞内蛋白质运输等;信号通路涉及MAPK信号传导途径;MCODE分析发现Cluster 1涉及TKT、ENO1、NCL、KIF1B等,参与调控驱动蛋白、雌激素的高尔基体运输;Cluster 2涉及SIN3B、PHF20、CTBP1、XPNPEP1等,参与调控组蛋白反应;心耳、左心室、肺的组织特异性PPI网络提示浙贝母-瓜蒌配伍可能通过调控ELAVL1-ENO1-NCL轴影响COPD并发HF进展;分子对接表明其“宽胸散结”主要活性成分瓜蒌酸、“化痰散结”主要成分贝母新碱与ELAVL1、ENO1、NCL蛋白质靶标的结合高度稳定,且贝母新碱与靶蛋白结合力强于瓜蒌酸,体现两者配伍后先治肺再调心,相须为用以实现心肺共治的作用特点。We used the Gene Expression Omnibus database to identify targets associated with chronic obstructive pulmonary disease(COPD)and heart failure(HF).Then,we explored the chemical composition and targets of Fritillaria thunbergii-Trichosanthis fructus to determine their potential to regulate COPD complicated by HF.We analyzed the target function and pathway annotation to create a network of tissue-specific protein-protein interactions(PPI).A total of 227 targets were involved in regulating COPD complicated by HF progression through Fritillaria thunbergii-Trichosanthis fructus,including 153 upregulated and 74 downregulated genes.Topological analysis showed that the average median of the PPI network was 0.4,and the average degree value was 1.83,with key targets including RPS23,SNU13,NOL6,ELAVL1.The cellular components were mainly located in the endomembrane system,nuclear endosomes,and extracellular vesicles.Biological processes mainly involved vesicle-mediated transport,microtubule-based motility,and intracellular protein transport.The relevant signaling pathway was the MAPK signaling pathway.MCODE analysis revealed two core clusters:Cluster 1 involves genes such as TKT,ENO1,NCL,and KIF1B,which are involved in regulating the Golgi transport of kinesin and estrogen,and Cluster 2 involves genes such as SIN3B,PHF20,CTBP1,and XPNPEP1,which are involved in the regulation of histone-associated responses.Tissue-specific PPI networks in the auricles,left ventricle,and lungs suggest that the Fritillaria thunbergii-Trichosanthis fructus pairing may affect the progression of COPD complicated by HF through the regulation of the ELAVL1-ENO1-NCL axis.Molecular docking showed that the binding of trichosanic acid,the main active ingredient involved in relieving the chest and dispersing mass,and peimisine,the main ingredient involved in dissipating phlegm and dispersing mass,to the protein targets ELAVL1,ENO1,and NCL was highly stable,and that the binding of peimisine to said three target proteins was stronger than that of trichosanic

关 键 词：浙贝母 瓜蒌 慢性阻塞性肺病 心脏衰竭 系统药理学 

分 类 号：R285[医药卫生—中药学]