网络药理学结合实验验证挖掘桑白皮-地骨皮干预急性肺损伤的活性成分及潜在机制  

Excavation of the Active Components and Potential Mechanisms of Mori Cortex Lycii Cortex Intervention in Acute Lung Injury with Network Pharmacology Combined with Experimental Validation

作　　者：张天宇 吴振起 刘光华[3] 赵炟 赵奚玉 于雪洁 梁翔宇 齐兆东 ZHANG Tianyu;WU Zhenqi;LIU Guanghua;ZHAO Da;ZHAO Xiyu;YU Xuejie;LIANG Xiangyu;QI Zhaodong(The First Clinical College of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China;The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,China;College of Traditional Chinese Medicine of Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学第一临床学院,辽宁沈阳110847 [2]辽宁中医药大学附属第二医院,辽宁沈阳110034 [3]辽宁中医药大学中医学院,辽宁沈阳110847

出　　处：《中国中医药信息杂志》2024年第11期42-50,共9页Chinese Journal of Information on Traditional Chinese Medicine

基　　金：国家自然科学基金面上项目(81874490、82074494);辽宁中医药大学附属第二医院“育苗工程”(2023-LZYY-1-05);辽宁省教育厅储备项目-优秀研究生项目(2024年)。

摘　　要：目的基于网络药理学、分子对接结合动物实验验证桑白皮-地骨皮药对干预急性肺损伤(ALI)的作用机制。方法利用TCMSP数据库获取桑白皮-地骨皮药对的活性成分,运用SwissTargetPrediction数据库进行活性成分靶点预测;应用GeneCards、DisGeNET数据库收集ALI疾病靶点;通过构建蛋白相互作用(PPI)网络筛选关键靶点,对关键靶点进行GO及KEGG通路富集分析;采用Cytoscape软件构建药物-成分-靶点-通路网络;采用AutoDock和PyMOL软件对核心活性成分及靶点进行分子对接。利用脂多糖建立ALI小鼠模型,对主要靶点和通路进行实验验证。结果获得桑白皮-地骨皮药对活性成分44个,作用靶点138个,其中干预ALI的潜在作用靶点26个,主要为TNF、EGFR、NFKB1、MPO、TNFRSF1A、NOX4等,关键通路为MAPK信号通路、IL-17信号通路、NF-κB信号通路等;分子对接结果显示,核心活性成分与主要靶点具有较强的结合活性;动物实验结果表明,中、高剂量桑白皮-地骨皮药对可有效改善ALI小鼠肺组织病理损伤,降低血清白细胞介素(IL)-6、肿瘤坏死因子(TNF)-α含量(P<0.01),升高IL-10含量(P<0.01);抑制肺组织EGFR、PI3K、AKT、NF-κB p65蛋白表达(P<0.01)。结论桑白皮-地骨皮药对中的槲皮素、蒙花苷等成分,作用于EGFR、TNF等靶点,通过EGFR/PI3K/NF-κB信号通路等多途径干预ALI。Objective To validate the mechanism of Mori Cortex-Lycii Cortex(MCLC)in intervening acute lung injury(ALI)based on network pharmacology,molecular docking combined with animal experiments.Methods The TCMSP database was used to obtain the active components of MCLC;the SwissTargetPrediction database was used to predict the targets of active components;the GeneCards database and DisGeNET database were used to collect the disease targets of ALI;the key targets were screened by constructing a PPI network,and the key targets were subjected to GO and KEGG pathway enrichment;a drug-component-target-pathway network was constructed using Cytoscape software;AutoDock and PyMOL software were used to validate the molecular docking of some of the compounds and targets;LPS was used to establish a mouse model of ALI for experimental validation,and experimental validation was performed to main targets and pathways.Results Totally 44 active components of MCLC and 138 action targets were obtained;26 potential targets of MCLC intervention in ALI were obtained,mainly TNF,EGFR,NFKB1,MPO,TNFRSF1A,NOX4,etc.,and the key pathways were MAPK signaling pathway,IL-17 signaling pathway,NF-κB signaling pathway,etc.;molecular docking results showed that the core active components of MCLC and the main targets had strong binding activities;animal experiments showed that MCLC at medium and high dosages could effectively improve the lung histopathological damage in ALI mice,decrease the contents of IL-6 and TNF-αin serum(P<0.01),and increase IL-10 content(P<0.01);MCLC inhibited protein expressions of EGFR,PI3K,AKT,NFκB p65 in lung tissue(P<0.01).Conclusion MCLC may intervene ALI by components such as quercetin and buddleoside,acting on targets including EGFR and TNF,through ulti-pathways of EGFR/PI3K/NF-κB signaling pathway,etc.

关 键 词：桑白皮-地骨皮 急性肺损伤 网络药理学 分子对接 机制 小鼠 

分 类 号：R285[医药卫生—中药学]