黄芪建中汤下调TLR-2、p-NF-κB表达治疗消化性溃疡的效应及机制研究  

Effect and mechanism of Huangqi Jianzhong Decoction on peptic ulcer by down-regulating TLR-2 and p-NF-κB expression

作　　者：仇婧玥 陈小娟 曾梅艳 喻昶 熊萌 宋厚盼[1,2] QIU Jing-yue;CHEN Xiao-juan;ZENG Mei-yan;YU Chang;XIONG Meng;SONG Hou-pan(Hunan Provincial Key Laboratory of Diagnostics of Traditional Chinese Medicine,Hunan University of Chinese Medicine;College of Traditional Chinese Medicine,Hunan University of Chinese Medicine,Changsha 410208,China)

机构地区：[1]湖南中医药大学中医诊断学湖南省重点实验室 [2]湖南中医药大学中医学院,长沙410208

出　　处：《天然产物研究与开发》2023年第3期477-488,共12页Natural Product Research and Development

基　　金：国家自然科学基金青年科学基金(81703920);湖湘青年科技创新人才项目(2021RC3101);湖南省教育厅科学研究重点项目(21A0240);湖南中医药大学研究生创新项目(2021CX46)。

摘　　要：本研究结合网络药理学、生物信息学与动物实验探究黄芪建中汤(HQJZD)治疗消化性溃疡(PU)的疗效与机制。运用中药系统药理学数据库和分析平台检索出HQJZD主要活性成分110个,预测靶点943个;基于疾病数据库TTD、OMIM、GAD、DrugBank、Pharm GKB共检索到与PU发病密切相关的靶点157个。运用Cytoscape筛选出HQJZD治疗PU的特异性靶点417个,GO和KEGG结果显示HQJZD可能通过调控Toll样受体、NF-κB、JAK-STAT、MAPK等信号通路介导的炎性反应发挥治疗效应。PU脾胃虚寒证大鼠胃黏膜的HE染色、酶联免疫吸附试验和免疫荧光染色结果表明,HQJZD低、高剂量组均能有效修复PU脾胃虚寒证大鼠的胃黏膜组织病理学损伤,显著升高PGE 2及NO含量(P<0.01),显著降低TLR2和p-NF-κB蛋白表达水平(P<0.05)。综上所述,HQJZD治疗PU具有多成分、多途径、多靶点的特点,其机制可能与调节PGE 2、NO等炎症因子水平,调控NF-κB信号通路和Toll样受体信号通路有关。In this study,we explored the mechanism of action and efficacy of Huangqi Jianzhong Decoction(HQJZD)in treating peptic ulcer(PU)using network pharmacology analysis and animal experiments.The Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP)was used to retrieve 110 active components of HQJZD and predict 943 targets.A total of 157 targets closely related to PU were retrieved from the disease databases TTD,OMIM,GAD,DrugBank and Pharm GKB.By using Cytoscape,417 specific targets for HQJZD for PU were identified.In GO and KEGG enrichment analyses,HQJZD may have a therapeutic role in regulating inflammatory reactions mediated by Toll-like receptors,NF-κB,JAK-STAT,MAPK and other factors.Based on HE staining,enzyme-linked immunosorbent assay,and immunofluorescence staining of rats with PU spleen stomach deficiency cold syndrome,HQJZD at low and high doses could effectively repair pathological damage to gastric mucosa,significantly increase PGE 2 and NO levels(P<0.01)and reduce TLR2 and p-NF-κB expression(P<0.05).As a result,HQJZD treatment of PU has the characteristics of being multi-component,multi-channel,and multi-target therapies.The mechanism of its action may involve regulating PGE 2 and NO levels,as well as the NF-κB signaling pathway and the Toll like receptor signaling pathway.

关 键 词：黄芪建中汤 消化性溃疡 分子机制 TOLL样受体 NF-ΚB 生物学实验 

分 类 号：R285.5[医药卫生—中药学]