当归贝母苦参丸治疗良性前列腺增生的作用机制研究  

Study on the Mechanism of Angelica Fritillaria Kushen Pills in the Treatment of Benign Prostatic Hyperplasia

作　　者：陈少峰 耿强[1] 赵丰 高瑞芳 李重[1] 孙远 张圆[3] 李春旭 Chen Shaofeng;Geng Qiang;Zhao Feng;Gao Ruifang;Li Zhong;Sun Yuan;Zhang Yuan;Li Chunxu(Department of Andrology,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moribustion,Tianjin 300193,China;Tianjin Institute of Medical Sciences,Tianjin 300131,China;Department of Pediatrics,First Teaching Hospital of Tianjin University of Traditional Chinese Medicine,National Clinical Research Center for Chinese Medicine Acupuncture and Moribustion,Tianjin 300193,China;Department of Urology,Tianjin Medical University Second Hospital,Tianjin 300211,China)

机构地区：[1]天津中医药大学第一附属医院男科,国家中医针灸临床医学研究中心,天津300193 [2]天津市医药科学研究所,天津300131 [3]天津中医药大学第一附属医院儿科,国家中医针灸临床医学研究中心,天津300193 [4]天津医科大学第二医院泌尿外科,天津300211

出　　处：《南开大学学报（自然科学版）》2022年第6期23-30,共8页Acta Scientiarum Naturalium Universitatis Nankaiensis

基　　金：天津市卫生健康委员会中医中西医结合科研课题(2021047,2021071);中国中医科学院科技创新工程(CI2021A02201)。

摘　　要：通过网络药理学及实验验证研究当归贝母苦参治疗良性前列腺增生的作用机制.通过TCMSP筛选当归贝母苦参丸的药物成分及靶点,运用Gene Cards、OMIM及Gis Ge NET检索BPH的疾病靶点,venny2.1筛出共同靶点.STRING分析并构建PPI,Metascape进行GO和KEGG分析.使用Cytoscape软件构建"成分-靶点-通路"网络图.建立良性前列腺增生大鼠模型,采用当归贝母苦参药液灌胃治疗,留取前列腺组织、称重,采用RT-PCR检测m RNA表达,WB检测靶点蛋白表达.研究发现当归贝母苦参中的31个有效成分通过多条通路直接作用于75个疾病靶点治疗良性前列腺增生,其中槲皮素、犀草素、β-谷甾醇、芒柄花黄素、豆甾醇、菜豆素、8-异戊烯基山柰酚等是核心成分,JUN、ESR1、TP53、AKT1、IL6、MAPK1、TNF、MAPK14、EGFR和VEGFA是至关重要的靶点.基因功能注释分析结果显示,交集基因最可能相关的生物过程主要涉及细胞对激素反应等,细胞组分主要涉及膜筏、膜微区等,分子功能主要涉及DNA结合转录因子结合、细胞因子活性、蛋白激酶结合等.通路富集分析结果提示当归贝母苦参主要参与脂类代谢、PI3K-AKT、HIF-1、MAPK、EGFR、雌激素等信号通路.动物实验结果,q RT-PCR检测显示ESR1、AKT1、IL6、MAPK1、EGFR m RNA表达量降低,Western blot (WB)检测显示ESR1、AKT1、IL6、MAPK1和EGFR蛋白表达量降低.当归贝母苦参丸主要通过调节脂类代谢、PI3K-AKT、HIF-1、MAPK、EGFR、雌激素等信号通路的ESR1、AKT1、IL6、MAPK1、EGFR等疾病靶点治疗良性前列腺增生.To study the mechanism of action of Angelica Fritillaria Kushen Pills in treating benign prostatic hyperplasia through network pharmacology and experimental verification. The drug ingredients and targets of Angelica Fritillaria Kushen Pills were screened by TCMSP, and the standardized name of uniprot was used;the disease targets of BPH were searched by GeneCards, OMIM and GisGeNET, and the common targets were screened out by venny 2.1. STRING analyzes and constructs PPI, Metascape performs GO and KEGG analysis. The component-target-pathway network diagram was constructed using Cytoscape software. Rat models of benign prostatic hyperplasia were established, treated with Angelica Fritillaria Sophora flavescens liquid by gavage, the prostate tissue was collected and weighed, mRNA expression was detected by qRT-PCR, and target protein expression was detected by Western blot. The study found that31 active ingredients in Angelica Fritillaria Sophora act directly on 75 disease targets through multiple pathways to treat benign prostatic hyperplasia, among which quercetin, rhinocerosin,β-sitosterol, formononetin,stigmasterol, phaseolin, 8-prenyl kaempferol, etc. are the core components, and JUN, ESR1, TP53,AKT1, IL6, MAPK1, TNF, MAPK14, EGFR, and VEGFA are the crucial targets. The results of gene function annotation analysis showed that the biological processes most likely related to the intersection genes mainly involved the response of cells to hormones, etc. The results of pathway enrichment analysis indicated that Angelica Fritillaria Sophora was mainly involved in lipid metabolism, PI3K-AKT, HIF-1,MAPK, EGFR, estrogen and other signaling pathways. As a result of animal experiments, PCR detection showed that the expression of ESR1, AKT1, IL6, MAPK1, and EGFR mRNA decreased, and WB detection showed that the expression of ESR1, AKT1, IL6, MAPK1, and EGFR protein decreased. Angelica Fritillaria Kushen Pills mainly treat benign prostatic hyperplasia by regulating lipid metabolism, PI3KAKT, HIF-1, MAPK, EGFR, estrogen and

关 键 词：当归贝母苦参丸 良性前列腺增生 网络药理学 作用机制 实验验证 

分 类 号：R961.1[医药卫生—药理学]