基于网络药理学探讨黄柏-王不留行药对治疗慢性非细菌性前列腺炎大鼠的作用机制  

Mechanism of Phellodendri Chinensis Cortex-Vaccariae Semen in the treatment of chronic non-bacterial prostatitis in rats based on network pharmacology

作　　者：党静静 于文涛 莫小萱 刘兴超 邓国兴 DANG Jing-jing;YU Wen-tao;MO Xiao-xuan;LIU Xing-chao;DENG Guo-xing(Hebei University of Chinese Medicine,Shijiazhuang 050200,China;Hebei Technology Innovation Center of TCM Formula Preparations;Hebei University Traditional Chinese Medicine Development and Industrial Application Technology Research and Development Center,Shijiazhuang 050091,China)

机构地区：[1]河北中医药大学,石家庄050200 [2]河北省中药组方制剂技术创新中心 [3]河北省高校中药开发与产业化应用技术研发中心,石家庄050091

出　　处：《天然产物研究与开发》2025年第3期544-554,536,共12页Natural Product Research and Development

基　　金：河北省自然科学基金(H2023423087);河北省中医药管理局资助项目(2019087)。

摘　　要：探讨黄柏-王不留行(Phellodendri Chinensis Cortex-Vaccariae Semen,PCC-VS)对慢性非细菌性前列腺炎(chronic non-bacterial prostatitis,CNP)炎性损伤的保护作用。本研究使用TCMSP及文献检索的方式筛选黄柏-王不留行中药有效成分41个、对应靶点蛋白156个;利用OMIM、GeneCards数据库筛选出9848个与CNP相关疾病靶点;使用Cystoscape、String软件构建蛋白靶点网络互作图(protein-protein interaction network,PPI)及药物-有效成分-疾病靶点-通路,PPI结果主要涉及白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumour necrosis factor-α,TNF-α)、白细胞介素-1β(interleukin-1 beta,IL-1β)、肿瘤蛋白p53(tumor protein-53,TP53)、丝氨酸/苏氨酸蛋白激酶(RAC-alpha serine/threonine-protein kinase,AKT1)等关键蛋白;使用Metascape对核心靶点蛋白基因进行基因本体(Gene Ontology,GO)富集分析和京都基因与基因组百科全书(Kyoto Encyclopedia of Genes and Genomes,KEGG)富集分析;KEGG富集通路主要涉及磷脂酰肌醇-3激酶/蛋白激酶B(phosphatidylinositol-3-kinase-protein kinase B,PI3K-AKT)、脂质与动脉粥样硬化、前列腺癌、丝裂原活化蛋白激酶(mitogen-activated protein kinase,MAPK)等信号通路;并将药物有效成分与核心靶点进行分子对接;为了验证以上数据,动物实验检测大鼠血清中IL-1β、白细胞介素-18(interleukin-18,IL-18)、TNF-α含量变化,对前列腺组织进行HE染色观察组织病理结构改变、蛋白免疫印迹(Western blot)检测药物与疾病相关的核心靶点蛋白IL-6、TNF-α、IL-1β及筛选出通路上相关蛋白表达。动物实验发现各给药组对炎症因子的调控及炎症相关蛋白的表达有抑制作用。研究结果表明,黄柏-王不留行通过多成分多靶点途径改善慢性非细菌性前列腺炎症状,可能与调控PI3K-AKT信号通路有关。To investigate the protective effect of Phellodendri Chinensis Cortex-Vaccariae Semen(PCC-VS)on inflammatory injury of chronic non-bacterial prostatitis(CNP).In this study,41 active ingredients and 156 corresponding target proteins were screened by TCMSP and literature search.OMIM and GeneCards databases were used to screen out 9848 disease targets related to CNP Cystoscape and String software were used to construct protein target network interaction map and active ingredient-disease target-pathway.PPI results mainly involved key proteins such as interleukin-6(IL-6),tumour necrosis factor-α(TNF-α),interleukin-1 beta(IL-1β),tumor protein-53(TP53)and RAC-alpha serine/threonine-protein kinase(AKT1).GO and KEGG pathway enrichment analysis were conducted using the Metascape database,enrichment of KEGG pathway involves PI3K-AKT,lipid and atherosclerosis,prostate cancer,MAPK signaling pathways;Molecular docking of active drug components and core targets was performed;In order to verify the above data,the serum levels of IL-1β,interleukin-18(IL-18),TNF-αin rats were detected in animal experiments.The pathological changes of prostate tissue were observed by HE staining.The core target proteins IL-6,TNF-α,IL-1βand the related proteins in the screened pathway were detected by Western blot.Animal experiments showed that the regulation of inflammatory factors and the expression of inflammation-related proteins were inhibited in each treatment group.These results suggest that the PI3K-AKT signaling pathway may be involved in the improvement of CNP through multi-component and multi-target pathways.

关 键 词：网络药理学 药对 慢性非细菌性前列腺炎 黄柏 王不留行 PI3K-AKT信号通路 

分 类 号：R285.5[医药卫生—中药学]