基于网络药理学及实验验证探讨吴茱萸汤减轻脓毒症大鼠肺损伤的作用机制  

Exploring the mechanism of Wuzhuyu decoction in reducing lung injury in sepsis rats based on network pharmacology and experimental validation

作　　者：金颂峰 邸静鑫 关玉娟[1] 丁晓欢[1] 甘雨[1] 崔英海[1] 张继伟 陈美娟 林宇康 于雪峰[1] 尹江涛 JIN Songfeng;DI Jingxin;GUAN Yujuan;DING Xiaohuan;GAN Yu;CUI Yinghai;ZHANG Jiwei;CHEN Meijuan;LIN Yukang;YU Xuefeng;YIN Jiangtao(The Second Affiliated Hospital of Liaoning University of Traditional Chinese Medicine,Shenyang 110034,China;Liaoning University of Traditional Chinese Medicine,Shenyang 110847,China)

机构地区：[1]辽宁中医药大学附属第二医院,辽宁沈阳110034 [2]辽宁中医药大学,辽宁沈阳110847

出　　处：《海南医科大学学报》2025年第6期433-442,共10页Journal of Hainan Medical University

基　　金：国家重点研发计划(2018YFC1707410);国家中医药管理局区域中医诊疗中心项目(中医肺病专业);国家中医药管理局中医药高质量发展协同创新转化工程项目(CXZH04);辽宁省自然科学基金计划项目[辽科发(2022)32号];于雪峰辽宁省名中医传承工作室建设项目[辽中医药发(2022)1号];辽宁省科技厅博士启动基金(2022‑BS‑068);沈阳市科学技术计划项目公共卫生研发专项(241002、240997);辽宁中医药大学附属第二医院“育苗工程”项目[辽中研发(2023)5号]。

摘　　要：目的:结合网络药理学与实验验证,探究吴茱萸汤减轻脓毒症大鼠肺损伤的可能机制。方法:采用TCMSP和ETCM数据库筛选并确定吴茱萸汤中活性成分,利用Uniport数据库挑选出有效靶标,借助GeneCards和OMIM数据库获取脓毒症肺损伤的疾病靶点,使用在线Venny平台选出二者的交集靶点,利用String平台构建PPI网络,运用Cytoscape 3.7.1软件筛选核心靶点,运用DAVID数据库进行GO及KEGG通路富集分析,构建“药物‑疾病‑通路”网络图。实验验证部分采用CLP法建立脓毒症肺损伤大鼠模型,药物干预后观察各组大鼠生存率及肺组织病理变化,比较肺组织湿/干重比,检测BALF中白细胞计数、相关炎症因子水平及肺组织中NF‑κB蛋白表达情况。结果:本研究共筛选得到TNF‑α、IL‑1β、IL‑6等159个吴茱萸汤治疗脓毒症‑肺损伤的作用靶点,涉及包括NF‑κB signaling pathway在内的20条关键通路。实验验证结果显示:各给药组较模型组大鼠生存率提高(P<0.05),其中吴茱萸汤中剂量组较其余给药组提高最显著(P<0.05);模型组较假手术组大鼠肺组织湿/干比升高(P<0.05),而各给药组较模型组下降(P<0.05),其中吴茱萸汤中剂量组较其余给药组下降最显著(P<0.05);模型组较假手术组BALF中白细胞计数及TNF‑α、IL‑1β、IL‑6水平均升高(P<0.05),而各给药组较模型组均降低(P<0.05),其中吴茱萸汤中剂量组较其余给药组降低最显著(P<0.05);模型组较假手术组大鼠肺组织中NF‑κB p65蛋白表达上调(P<0.05),而各给药组较模型组下调(P<0.05),其中吴茱萸汤中剂量组较其余给药组下调最显著(P<0.05)。结论:吴茱萸汤可降低TNF‑α、IL‑1β、IL‑6水平,下调NF‑κB蛋白表达,通过抑制脓毒症大鼠炎症以减轻肺损伤,该作用机制可能与NF‑κB信号通路有关。Objective:To pharmacology and experimental verification explore the possible mechanism of Wuzhuyu decoction in reducing lung injury in septic rats based on network.Methods:TCMSP and ETCM databases were used to screen and determine the active ingredients in Wuzhuyu decoction.Effective targets were selected using the Uniport database,and disease targets for sepsis-induced lung injury were obtained using GeneCards and OMIM databases.The intersection targets of the two were selected using the online Venny platform.A PPI network was constructed using the String platform,and core targets were screened using Cytoscape 3.7.1 software.The DAVID database was utilized to analyze GO and KEGG pathway and a"Drug‑Disease‑Pathway"network diagram was constructed.The experimental validation section used the CLP method to establish a rat model of sepsisinduced lung injury.After drug intervention,the survival rate and pathological changes in lung tissue of each group of rats were observed,and the wet/dry weight ratio of lung tissue was compared.The white blood cell count,levels of related inflammatory factors in BALF and expression of NF‑κB protein in lung tissue were detected.Results:This research screened 159 targets of Wuzhuyu decoction for the cure of sepsis lung injury,including TNF‑α,IL‑1β,IL‑6,etc,involving 20 key pathways including NF‑κB signaling pathway.The experimental verification results showed that the survival rates of rats in each treatment group were im‑proved compared to the model group(P<0.05),while the medium dose group of Wuzhuyu decoction showed the most significant improvement compared to the other treatment groups(P<0.05).The wet/dry ratio of lung tissue in the model group was higher than the sham surgery group(P<0.05),while each treatment group showed a decrease compared to the model group(P<0.05).Among them,the medium dose group of Wuzhuyu decoction showed the most significant decrease compared to the other treatment groups(P<0.05).The model group showed an increase in white blood cell c

关 键 词：吴茱萸汤 脓毒症 肺损伤 抗炎 网络药理学 

分 类 号：R285.5[医药卫生—中药学]