基于网络药理学与分子对接方法探讨附子治疗大肠杆菌感染型犊牛腹泻的作用机制  

Based on Network Pharmacology and Molecular Docking Method to Explore the Mechanism of Aconite in the Treatment of E.coli Infected Calf Diarrhea

作　　者：钱英红 张静 赵俊利 刘向敏 吉鹏华 王超 张兴夫 Qian Yinghong;Zhang Jing;Zhao Junli;Liu Xiangmin;Ji Penghua;Wang Chao;Zhang Xingfu(Academy of Agricultural and Animal Husbandry Sciences of Inner Mongolia Autonomous Region,Hohhot,010010,Inner Mongolia;Veterinary College of Inner Mongolia Agricultural University,Hohhot,010018,Inner Mongolia;Key Laboratory of Clinical Diagnosis and Treatment of Animal Diseases,Ministry of Agriculture and Rural Affairs,Hohhot,010018,Inner Mongolia)

机构地区：[1]内蒙古自治区农牧业科学院,内蒙古呼和浩特010010 [2]内蒙古农业大学兽医学院,内蒙古呼和浩特010018 [3]农业农村部动物疾病临床诊疗技术重点实验室,内蒙古呼和浩特010018

出　　处：《中国畜禽种业》2024年第6期94-102,共9页The Chinese Livestock and Poultry Breeding

基　　金：内蒙古农牧业青年创新基金项目-内蒙古自治区犊牛腹泻大肠杆菌的分离鉴定与耐药性分析(2021QNJJM10)。

摘　　要：该文通过TCMSP数据库对附子的主要化学成分进行筛选并确定其主要成分的潜在靶点,于GeneCard和Dis-GeNET查找犊牛腹泻的相关靶点取交集,得到附子防治奶牛子宫内膜炎的关键靶点,并构建蛋白互作(PPI)网络;通过DAVDE数据库对核心靶点进行GO功能与KEGG通路富集分析;通过AutoDock软件对分子和靶点对接,并运用Py MOL对分子结果进行可视化处理。结果表明:从该中药复方中筛选出有效活性成分主要包括石防风素、苯甲酰萘普林、新糖尿酸B、 11,14-二十碳二烯酸等,这些药物成分主要作用靶点426个,犊牛腹泻的相关靶点1330个。附子防治奶牛乳房炎有136个预测靶点,主要包括白细胞介素6、胱天蛋白酶3、表皮生长因子受体、核激素受体、基质金属蛋白激酶9等。对上述136个靶点进行富集分析,发现与炎症反应、血管内皮生长因子、 ERK1和ERK2级联的正调控等生物过程;一氧化氮合酶活性、类固醇的结合、锌离子结合等细胞组分;细胞外基质、胞浆和细胞核等分子功能,以及PI3K-Akt信号通路、内分泌失调、 TNF信号通路、 IL-17信号通路和癌症等通路相关。分子对接结果表明复方双黄连主要活性成分Deltoin和Benzoylnapelline均与关键靶点IL-6、CASP3具有良好的连接活性。可见,附子可通过多成分、多靶点和多通路共同来防治大肠杆菌引起的犊牛腹泻。The main chemical components of aconite were screened through the TCMSP database and the potential targets of the main components were determined.The key targets of the aconite in the prevention and treatment of endometritis in dairy cows were obtained by searching for the intersection of related targets of calf diarrhea on GeneCard and DisGeNET,and the protein interaction(PPI)network was constructed.The DAVDE database was used to analyze the GO function and KEGG pathway enrichment of the core targets.Molecules and targets were docked through AutoDock software,and molecular results were visualized using PyMOL.The effective active ingredients were mainly Deltoin,Benzoylnapelline and Neokadsuranic acid B(neoglycerynic acid B),11,14-eicosadienoic acid(11,14-eicosadienoic acid),etc.,these drug components have 426 main targets,and 1330 related targets of calf diarrhea.There are 136 predicted targets for the prevention and treatment of dairy cow mastitis by aconite,mainly including IL-6(interleukin 6),CASP3(caspase 3),EGFR(epidermal growth factor receptor),ESR1(nuclear hormone receptor),MMP9(matrix metalloprotein kinase 9),etc.The enrichment analysis of the above 136 targets revealed the positive regulation of inflammatory response,vascular endothelial growth factor,ERK1 and ERK2 cascades,etc.nitric oxide synthase activity,steroid binding,zinc ion binding and other cellular components;Molecular functions such as extracellular matrix,cytoplasm,and nucleus,as well as PI3K-Akt signaling pathway,endocrine disorders,TNF signaling pathway,IL-17 signaling pathway,and cancer pathways.The molecular docking results showed that the main active components of Deltoin and Benzoylnapelline had good linking activity with the key targets IL-6 and CASP3.It can be seen that aconite can prevent and treat calf diarrhea caused by Escherichia coli through multi-component,multi-target and multi-pathway.

关 键 词：中药 网络药理学 分子对接 犊牛腹泻 作用机制 

分 类 号：S858.23[农业科学—临床兽医学]