| 引用本文:郭宵飞1，张平1，白建琦1，杨晨1，李静静1，欧阳琴1，邓晓曦1，郭家敏1，朱冬菊2，王源1.固本解毒方调控肺腺癌免疫微环境的分子机制研究及实验验证[J].世界中医药,2023,(20):. |
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| 固本解毒方调控肺腺癌免疫微环境的分子机制研究及实验验证 |
| Molecular Mechanism of Guben Jiedu Prescription in Regulating Immune Microenvironment of Lung Adenocarcinoma and Experimental Verification |
| 投稿时间：2023-06-29 |
| DOI：10.3969/j.issn.1673-7202.2023.20.001 |
| 中文关键词: 固本解毒方 肺腺癌 免疫微环境 网络药理学 分子对接 实验验证 靶点 拓扑分析 |
| English Keywords:Guben Jiedu Prescription Lung adenocarcinoma Immune microenvironment Network pharmacology Molecular docking Experimental verification Target Topological analysis |
| 基金项目:国家自然科学基金项目（82174415)；中国中医科学院科技创新工程项目（CI2021A01818，CI2021A05054）；中国中医科学院望京医院基础研究苗圃培育计划课题（WJYY-YJKT-2022-07） |
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| 中文摘要: |
| 目的：通过网络药理学探究固本解毒方干预肺腺癌免疫微环境的作用机制，并通过动物实验验证。方法：通过中药系统药理学数据库与分析平台（TCMSP）等数据库筛选出固本解毒方的候选化学成分及其相关靶点，利用疾病靶点数据库获取肺腺癌及肿瘤免疫微环境的相关靶点，取交集后获得潜在作用靶点；运用蛋白质-蛋白质相互作用（PPI）分析数据库（STRING）建立PPI网络，以Cytoscape软件构建“中药-活性成分-靶点”网络图。最后，通过分子对接及动物实验进行结果验证。结果：共获得固本解毒方的候选活性成分251种，潜在作用靶点217个；中药的核心有效成分包括槲皮素（Quercetin）、β-谷甾醇（Beta-sitosterol）等，关键潜在作用靶点为促分裂原活化的蛋白激酶1(MAPK1)、促分裂原活化的蛋白激酶3（MAPK3）、信号转导及转录激活因子3(STAT3)、促分裂原活化的蛋白激酶14(MAPK14)；所涉及的主要信号通路主要包括磷脂酰肌醇-3-激酶-蛋白激酶B（PI3K-AKT）、促分裂原活化的蛋白激酶（MAPK)等信号通路；分子对接结果显示Beta-sitosterol与各核心潜在作用靶点均有良好结合活性；动物实验证明，固本解毒方能有效抑制STAT3、MAPK1、MAPK3蛋白的表达，激活MAPK14蛋白的表达。结论：固本解毒方可能是通过激活或抑制MAPK14、STAT3、MAPK1、MAPK3等核心潜在作用靶点的表达，调控PI3K-AKT、MAPK等多条信号通路，从而干预肺腺癌免疫微环境。 |
| English Summary: |
| This paper aims to explore the mechanism of Guben Jiedu Prescription in intervening with the immune microenvironment of lung adenocarcinoma by network pharmacology and verify it through animal experiments.Methods:The candidate chemical components and their related targets of Guben Jiedu Prescription were screened through the Chinese Medicine System Pharmacology Database and Analysis Platform(TCMSP) and other databases.The related targets of lung adenocarcinoma and tumor immune microenvironment were obtained by the disease target database，and the potential targets were obtained through the intersection.The STRING database was analyzed by protein-protein interaction(PPI) to establish a PPI network.Cytoscape software was used to build a “Chinese medicine-active ingredients-targets” network diagram.Finally，through molecular docking and animal experiments，the results were verified.Results:A total of 251 candidate active ingredients and 217 potential targets of Guben Jiedu Prescription were obtained.The core active ingredients of traditional Chinese medicine included quercetin，beta-sitosterol，etc.The key potential targets were mitogen-activated protein kinase 1(MAPK1)，mitogen-activated protein kinase 3(MAPK3)，signal transducer and activator of transcription 3(STAT3)，and mitogen-activated protein kinase 14(MAPK14).The main signaling pathways involved included phosphatidyl inositol-3-kinase-protein kinase B(PI3K-AKT) and MAPK signaling pathways.The molecular docking results showed that beta-sitosterol had good binding activity with all core potential targets.The animal experiments showed that Guben Jiedu Prescription could effectively inhibit the expression of STAT3，MAPK1，and MAPK3 proteins and activate MAPK14 protein expression.Conclusion:Guben Jiedu Prescription may regulate PI3K-AKT，MAPK，and other signaling pathways by activating or inhibiting the expression of core potential targets such as MAPK14，STAT3，MAPK1，and MAPK3，so as to interfere with the immune microenvironment of lung adenocarcinoma. |
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