基于网络药理学的柴芩承气汤调控TLR4/NF-κB通路防治重症急性胰腺炎机制研究  

Exploring Mechanism of Chai Qin Chengqi Decoction Treating Severe Acute Pancreatitis by Regulating TLR4/NF-κB Pathway Based on Network Pharmacology

作　　者：党琳[1] 崔亚亚[1] 宋亮[1] 段丽芳[1] 张红[1] DANG Lin;CUI Yaya;SONG Liang;DUAN Lifang;ZHANG Hong(Shaanxi University of Chinese Medicine,Xianyang 712046 Shaanxi,China)

机构地区：[1]陕西中医药大学,陕西咸阳712046

出　　处：《中药新药与临床药理》2019年第9期1032-1038,共7页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金资助项目（81603420）;陕西省教育厅2018重点科学研究计划项目（18JS029）;陕西省科技厅社会发展科技攻关项目（2015SF222）;陕西省教育厅专项科研计划项目（16JK1197）

摘　　要：目的基于网络药理学的方法预测柴芩承气汤(Chai Qin Chengqi decoction,CQCQD)治疗重症急性胰腺炎(Severe acute pancreatitis,SAP)的有效成分、潜在靶点及通路,结合动物实验探讨其治疗SAP的作用机制。方法利用中药系统药理数据库(TCMSP)筛选出柴芩承气汤复方中化合物的有效成分群,针对SAP发病机制,通过Pharm Mapper服务器进行靶点的预测分析。将得到的潜在靶点导入MAS 3.0数据库进行靶点注释与分析,最后结合KEGG数据库进行通路分析,采用Cytoscape软件构建柴芩承气汤治疗SAP的'化合物-靶点-通路'网络模型。筛选出与SAP相关性高的'药物-靶点-通路',继而采用L-精氨酸(L-Arg)诱导复制SAP小鼠模型,并给予柴芩承气汤灌胃,验证柴芩承气汤对SAP小鼠的治疗作用及其对高相关性靶点通路的调控作用。结果共预测得到柴芩承气汤潜在靶点558个和42条信号通路,其中有12个靶点和28条信号通路与SAP相关,包括在SAP中对炎症因子具有调控作用的Toll样受体(Toll-like receptor,TLR)信号通路。动物实验验证结果表明,柴芩承气汤可通过对TLR4及其下游重要介质NF-κB的调节达到对SAP的治疗作用。结论柴芩承气汤通过'多成分、多靶点、多通路'协同发挥抗SAP的作用,其中TLR4/NF-κB是其作用的主要靶点之一。Objective To explore the mechanism of Chai Qin Chengqi decoction(CQCQD)in the treatment of severe acute pancreatitis(SAP)by predicting the effective components,potential targets and pathways of CQCQD using the network combining experimental pharmacology approaches.Methods The active ingredients of CQCQD were screened using the Traditional Chinese Medicine System Pharmacology Database(TCMSP).The predictive analysis of targets was conducted by PharmMapper server according to the pathogenesis of SAP.The obtained potential targets were imported into the MAS3.0 database for target annotation and analysis;the pathway enrichment analysis was performed using Kyoto Encyclopedia of Genes and Genomes(KEGG)database.Finally,the'component-target-pathway'network model of CQCQD in the treatment of SAP was constructed using Cytoscape software.Moreover,high-related pathways were tested in the L-Arg-induced SAP animal model for verification the therapeutic effect of CQCQD and its regulation of highly-related pathways.Results A total of 558 potential targets and 42 signaling pathways were predicted for CQCQD,among which 12 targets and 28 signaling pathways were associated with SAP,including toll-like receptor(TLR)signaling pathway that regulates inflammatory factors in SAP.The animal experiments further confirmed the therapeutic effect of CQCQD on SAP through the regulation of TLR4 and its downstream NF-κB pathway.Conclusion CQCQD plays a protective role on SAP through'multicomponent,multi-target,multi-pathway',among them TLR4/NF-κB is one of the main targets.

关 键 词：网络药理学 柴芩承气汤 重症急性胰腺炎 靶点预测 作用机制 TLR4/NF-κB 

分 类 号：R285.5[医药卫生—中药学]