清宣解毒颗粒治疗流感病毒致急性肺损伤的作用机制研究  

Mechanism of Qingxuan Jiedu Granules in the Treatment of Acute Lung Injury Induced by Influenza Virus

作　　者：李丹婷 王泽琨 姚妙诗 王雯蕾 郑志慧 张评浒 束雅春 LI Danting;WANG Zekun;YAO Miaoshi;WANG Wenlei;ZHENG Zhihui;ZHANG Pinghu;SHU Yachun(Affiliated Hospital of Nanjing University of Chinese Medicine·Jiangsu Provincial Hospital of Traditional Chinese Medicine,Nanjing,Jiangsu,China 210029;Institute of Transnational Medicine·Jiangsu Key Laboratory of Integrated Traditional Chinese and Western Medicine for Prevention and Treatment of Senile Diseases,Medical College,Yangzhou University,Yangzhou,Jiangsu,China 225009;Jiangsu Province Seaside Rehabilitation Hospital,Lianyungang,Jiangsu,China 222042)

机构地区：[1]南京中医药大学附属医院·江苏省中医院,江苏南京210029 [2]扬州大学医学院转化医学研究院·江苏省中西医结合老年病防治重点实验室,江苏扬州225009 [3]江苏省海滨康复医院,江苏连云港222042

出　　处：《中国药业》2024年第19期51-58,共8页China Pharmaceuticals

基　　金：江苏省知识产权战略推进计划项目[GJ20231160_01];江苏省研究生实践创新计划项目[SJCX22_0759];南京中医药大学自然科学基金[XZR2020020]。

摘　　要：目的探讨清宣解毒颗粒治疗流感病毒致急性肺损伤(ALI)的作用机制。方法分别制备甲型流感病毒致ALI模型小鼠、脂多糖(LPS)致ALI模型小鼠,经药物干预后,观察清宣解毒颗粒对小鼠肺部病变程度、肺指数及小鼠体质量和饮食量变化的影响。通过TCMSP,PubChem,SwissTargetPrediction数据库获得清宣解毒颗粒中桑叶、连翘、金银花等13味中药的有效成分及其对应靶点,通过GeneCards数据库检索获得与流感病毒致ALI相关的疾病靶点,通过Venny网站构建药物活性成分-疾病共有靶点;通过String数据库构建共有靶点蛋白质-蛋白质交互作用(PPI)网络,根据度值筛选核心靶点;通过Cytoscape 3.6.1软件构建药物-成分-核心靶点网络;通过Metascape数据库对核心靶点进行基因生物过程本体论(GO)功能分析、京都基因与基因组百科全书(KEGG)通路富集分析。结果清宣解毒颗粒具有改善甲型流感病毒致ALI模型小鼠肺部病变的趋势,也有减缓LPS致ALI小鼠体质量下降的趋势。通过网络药理学预测得到清宣解毒颗粒的活性成分173种,其中槲皮素、(-)-表没食子儿茶素没食子酸酯、木犀草素、山柰酚、甘乌内酯等可能是治疗流感病毒致ALI的关键成分,预测到信号转导和转录激活因子3、原癌基因酪氨酸蛋白激酶、丝氨酸/苏氨酸蛋白激酶1、丝裂原活化蛋白激酶3、肿瘤坏死因子(TNF)等可能是清宣解毒颗粒治疗流感病毒致ALI的潜在作用靶点;获得清宣解毒颗粒治疗流感病毒致ALI的甲型流感、磷脂酰肌醇-3-激酶(PI3K)-Akt、TNF、C型凝集素受体、T淋巴细胞受体等信号通路。结论清宣解毒颗粒可能对ALI具有一定治疗作用,其作用机制可能是通过多种成分调控PI3K-Akt、TNF、C型凝集素受体等信号通路有关。Objective To investigate the mechanism of Qingxuan Jiedu Granules in the treatment of acute lung injury(ALI)induced by influenza virus.Methods ALI model mice induced by influenza A virus and ALI model mice induced by lipopolysaccharide(LPS)were prepared.After drug intervention,the effects of Qingxuan Jiedu Granules on the lung lesion severity,lung index,and changes in body weight and food intake in mice were observed.The effective ingredients and corresponding targets of 13 traditional Chinese medicines including Mori Folium,Forsythiae Frutus,and Lonicerae Flos in Qingxuan Jiedu Granules were obtained through TCMSP,PubChem,and SwissTargetPrediction databases,the disease targets related to influenza virus-induced ALI were retrieved through GeneCards database,the Venny website was used to construct the drug active-disease target network.The protein-protein interaction(PPI)network of common targets was constructed through the String database.Core targets were screened based on degree values.Drug-Component-core target network was constructed by the Cytoscape 3.6.1 software.Gene Ontology(GO)functional analysis and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis were conducted on the core targets through the Metascape database.Results Qingxuan Jiedu Granules exhibited a tendency to improve lung lesions in mice with ALI induced by the influenza A virus,and also showed a trend towards mitigating weight loss in mice with ALI induced by LPS.Through network pharmacology prediction,173 active ingredients of Qingxuan Jiedu Granules were identified,among which quercetin,(-)-epigallocatechin-3-gallate,luteolin,kaempferol,and gallic acid lactone might be key components in the treatment of lung injury induced by influenza.Signal transducer and activator of transcription 3(STAT3),proto-oncogene tyrosine-protein kinase Src(SRC),RAC-alpha serine/threonine-protein kinase(AKT1),mitogen-activated protein kinase 3(MAPK3),and tumor necrosis factor(TNF)were predicted to be potential targets for Qingxuan Jiedu Gran

关 键 词：急性肺损伤 甲型流感 清宣解毒颗粒 作用机制 网络药理学 

分 类 号：R932[医药卫生—生药学] R285.5[医药卫生—药学]