基于网络药理学探讨柴胡口服液调治家禽热应激的分子机理  

Discussion on molecular mechanism of Radix Bupleuri oral liquid in regulating heat stress in poultry based on network pharmacology

作　　者：刘逸雷 丁康宁 邱文才 李伟豪 何永明 唐陆平 刘玉清 LIU Yilei;DING Kangning;QIU Wencai;LI Weihao;HE Yongming;TANG Luping;LIU Yuqing(School of Life Science and Engineering,Foshan University,Foshan 528231,China)

机构地区：[1]佛山科学技术学院生命科学与工程学院,广东佛山528231

出　　处：《黑龙江畜牧兽医》2021年第16期109-115,153,154,共9页Heilongjiang Animal Science And veterinary Medicine

基　　金：广东省自然科学基金项目(2017A030310607);广东省科技攻关计划项目(2015A040404048);畜禽疫病监测与综合防控共性关键技术研发创新团队项目(2019KJ119);广东省天然生物功能性饲料添加剂工程技术研究中心项目(2017GCZX006);佛山科学技术学院研究生自由探索基金项目(2020ZYTS48)。

摘　　要：为了探讨柴胡口服液在调治家禽热应激中的靶点与通路,试验通过TCMSP数据库检索柴胡中主要活性成分及其对应的靶点,根据ADME属性筛选中药活性成分;通过GeneCards、OMIM、TTD、DisGENET数据库获取热应激主要靶点;利用STRING11.0平台进行蛋白质相互作用分析,构建蛋白质互作网络;运用DAVID平台分析"药物-成分-靶点"及其参与的GO生物学过程与KEGG信号通路;采用Cytoscape 3.8.0软件构建"柴胡活性成分-热应激靶点-KEGG通路"网络图,并进行动物试验验证网络药理学预测得到的结果。结果表明:柴胡口服液调治家禽热应激的核心活性成分为槲皮素、山奈酚和异鼠李素等;其主要作用的核心靶点为RELA、IL-6、JUN、PTGS2、CHUK、NFKBIA、RAF1、HSP90AA1、CCND1和EGFR;柴胡口服液主要通过作用于MAPK、Toll样受体、Jak-STAT信号通路等炎性通路调节家禽热应激;热应激能激活MAPK信号通路中的ERK1/2、JNK和P38蛋白,而柴胡可极显著降低MAPK信号通路中上述蛋白质的表达(P<0.01)。说明热应激主要通过引起炎症反应而影响家禽的内环境平衡,而柴胡口服液可通过多靶点、多通路缓解热应激对家禽造成的影响。In order to discuss the targets and pathways of Radix Bupleuri oral liquid in regulating heat stress in poultry,the experiment retrieved the main active ingredients in Radix Bupleuri and their corresponding targets through the TCMSP database,and the active ingredients of traditional Chinese medicine according to ADME attributes were screened.The main targets of heat stress were obtained through GeneCards,OMIM,TTD,and DisGENET databases.The STRING11.0 platform for the analysis of protein interactions was used,and a protein interaction network was built.The DAVID platform was used to analyze the"drug-ingredient-target",the involved GO biological process and the KEGG signal pathway analysis.Cytoscape 3.8.0 software was used to construct a network diagram of"Radix Bupleuri active ingredient-heat stress target-KEGG pathway",and animal experiments were performed to verify the results of network pharmacology predictions.The results showed that the core active ingredients of Radix Bupleuri oral liquid in regulating heat stress in poultry were quercetin,kaempferol and isorhamnetin.The main core targets were RELA,IL-6,JUN,PTGS2,CHUK,NFKBIA,RAF1,HSP90 AA1,CCND1 and EGFR.Radix Bupleuri oral liquid mainly regulated poultry heat stress by acting on inflammatory pathways such as MAPK,Toll-like receptor,and Jak-STAT signal pathway.Heat stress could activate ERK1/2,JNK and P38 proteins in the MAPK signal pathway,and Radix Bupleuri could extremely significant reducted the expression of these proteins in the MAPK signal pathway(P<0.01).The results suggested that heat stress mainly affected the internal environment of poultry by causing inflammation,and Radix Bupleuri oral liquid could alleviate the impact of heat stress on poultry through multiple targets and multiple pathways.

关 键 词：热应激 网络药理学 柴胡 家禽 靶点预测 

分 类 号：S859.3[农业科学—临床兽医学] S859.7[农业科学—兽医学]