双石通淋胶囊治疗良性前列腺增生的网络药理学及实验研究  

Mechanism of Shuangshi Tonglin Capsules(双石通淋胶囊)against Benign Prostatic Hyperplasia:Based on Network Pharmacology and Experiment

作　　者：毛茜 王子强 王川 刘继平[1,2] 慕雅楠 卫昊 MAO Qian;WANG Ziqiang;WANG Chuan;LIU Jiping;MU Yanan;WEI Hao(College of Pharmacy,Shaanxi University of Chinese Medicine,Xianyang 712046;Key Laboratory of Pharmacodynamic Mechanism and Material Basis of Traditional Chinese Medicine,Shaanxi Administration of Traditional Chinese Medicine,Xianyang 712046)

机构地区：[1]陕西中医药大学药学院,咸阳712046 [2]陕西省中医药管理局中药药效机制与物质基础重点研究室,陕西712046

出　　处：《中药药理与临床》2023年第5期15-21,共7页Pharmacology and Clinics of Chinese Materia Medica

基　　金：国家自然科学基金(编号:81800401);陕西省重点研发计划(编号:2022SF-435);大学生创新创业训练计划项目(编号:S202210716022)。

摘　　要：目的:基于网络药理学及动物实验探讨双石通淋胶囊治疗良性前列腺增生(BPH)的作用机制。方法:通过TCMSP、SymMap和ETCM数据库筛选双石通淋胶囊的化学成分及靶点;利用GeneCards、DisGeNET和DrugBank数据库检索BPH疾病靶点;用STRING数据库构建蛋白互作网络;对关键靶点进行GO和KEGG富集分析;利用Cytoscape 3.7.2软件构建“双石通淋胶囊-活性成分-靶点-通路”图。分子对接预测核心成分与靶点的结合能力。采用去势联合皮下注射丙酸睾酮建立大鼠前列腺增生模型,造模同时进行灌胃干预,连续28 d,末次给药24 h后,比较各组大鼠体质量、前列腺湿质量及指数;HE染色和Masson染色观察前列腺组织病理变化和胶原沉积情况;Western blot法检测大鼠前列腺组织中EGFR、VEGFA、p-P38、p-AKT蛋白的表达。结果:双石通淋胶囊筛选出193种活性成分,包括槲皮素、木犀草素、汉黄芩素、黄芩素、薯蓣皂素、等核心成分,对应靶点422个,与994个疾病靶点取交集后得到100个共同靶点,核心靶点包括AKT1、STAT3、EGFR、CASP3、VEGFA、等;GO富集分析发现生物途径主要包括酶结合、转录因子结合、蛋白激酶结合、等;细胞组分主要包括大分子络合物、转录因子复合物、核染质、等;分子功能包括酶结合、序列特异性DNA结合、转录因子结合、等;KEGG富集分析发现MAPK信号通路、PI3K/AKT信号通路等可能在双石通淋胶囊治疗良性前列腺增生中起关键作用。分子对接结果显示,汉黄芩素与VEGFA结合能力最强。HE和Masson染色显示,与假手术对照组相比,模型对照组大鼠前列腺组织增生及胶原沉积明显;与模型对照组相比,双石通淋胶囊2.5 g/kg组大鼠前列腺湿质量和指数明显降低(P<0.05);给药各组大鼠前列腺中EGFR、VEGFA、p-AKT、p-P38蛋白表达明显下调(P<0.05或P<0.01),给药各组的前列腺增生程度及胶原沉积明显减轻。结论:双石通淋胶囊通Objective:To investigate the mechanism of Shuangshi Tonglin Capsules(双石通淋胶囊)(SSTLC)against benign prostatic hyperplasia(BPH)based on network pharmacology and animal experiment.Methods:Components and targets of SSTLC were retrieved from Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP),SymMap,and Encyclopedia of Traditional Chinese Medicine(ETCM).BPH-related targets were searched form GeneCards,DisGeNET,and DrugBank.STRING was used to predict the protein-protein interactions.Gene Ontology(GO)term and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment of the key targets were performed,and SSTLC-active component-target-pathway network was constructed with Cytoscape 3.7.2.Molecular docking was used to predict the binding ability of core components to targets.Castration combined with subcutaneous injection of testosterone propionate was employed to induce prostatic hyperplasia in rats.Administration(gavage)was performed while modeling for 28 days.The body weight,wet weight of prostate,and prostate index were compared 24 h after the last administration.Based on hematoxylin and eosin(HE)staining and Masson staining,the pathological changes and collagen deposition of prostate tissue were observed.The protein expression of epidermal growth factor receptor(EGFR),vascular endothelial growth factor A(VEGFA),phosphorylated(p)-P38,and p-protein kinase B(AKT)in rat prostate tissues was measured by Western blotting.Results:A total of 193 active components of SSTLC were screened out,including quercetin,luteolin,wogonin,baicalein,and diosgenin,and 422 targets of the components were retrieved.The components and the disease(994 targets)shared 100 targets which consisted of AKT1,signal transducer and activator of transcription 3(STAT3),EGFR,caspase-3(CASP3),and VEGFA.The key targets were involved in the major biological processes of enzyme binding,transcription factor binding,and protein kinase binding,cellular components of macromolecular complex,transcription factor com

关 键 词：双石通淋胶囊 良性前列腺增生 蛋白激酶 血管内皮因子 表皮生长因子受体 

分 类 号：R285.5[医药卫生—中药学]