| 引用本文:刘琴1，宋厚盼1，罗倩1，陈思清1，韩运宗1，周姝1，周赛男2.黄芪建中汤干预胃溃疡的药理实验及分子生物学作用机制[J].世界中医药,2024,(09):. |
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| 黄芪建中汤干预胃溃疡的药理实验及分子生物学作用机制 |
| Pharmacological Experiment and Molecular Biological Mechanism of Huangqi Jianzhong Decoction in Intervening Gastric Ulcer |
| 投稿时间：2023-01-09 |
| DOI：10.3969/j.issn.1673-7202.2024.09.002 |
| 中文关键词: 黄芪建中汤 胃溃疡 分子生物学 网络药理学 磷脂酰肌醇3-激酶 蛋白激酶B Wistar大鼠 |
| English Keywords:Huangqi Jianzhong Decoction Gastric ulcer Molecular biology Network pharmacology PI3K AKT Wistar rats |
| 基金项目:国家自然科学基金项目(81703920)；湖南省自然科学基金科卫联合项目（2022JJ70031）；湖南省中医药科研计划重点项目（2021203）；湖南中医药大学中医学一流学科开放基金重点项目（4901020000200222）；湖南中医药大学校级科研项目（2018XJJJ45） |
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| 中文摘要: |
| 目的：基于生物信息学分析黄芪建中汤治疗胃溃疡（GU）的作用机制，并结合动物实验进一步验证。方法：在中药系统药理学数据库与分析平台(TCMSP)、成分靶点预测数据库（Swiss Target Prediction）中收集黄芪建中汤的活性成分和作用靶点；利用基因数据库（GeneCards）、药物数据库（Drug Bank）等提取GU疾病靶点；在Cytoscape 3.7.2软件中获取黄芪建中汤防治GU的“活性成分-潜在治疗靶点”图，借助STRING和DAVID数据库依次获取蛋白质-蛋白质相互作用（PPI）网络、基因本体（GO）和基因组百科全书（KEGG）富集分析；并通过分子对接和动物实验验证黄芪建中汤防治GU的可能机制。结果：黄芪建中汤治疗GU有131个潜在靶点，其中核心靶点为磷脂酰肌醇-4,5-二磷酸3-激酶催化亚基α（PIK3CA）、蛋白激酶B1（AKT1）等，KEGG分析提示磷脂酰肌醇3-激酶/蛋白激酶B（PI3K/AKT）等信号通路发挥着重要作用。分子对接提示核心靶点与核心成分对接良好。动物实验显示，与正常组比较，模型组溃疡指数增高、胃组织出现炎性浸润，白细胞介素-6（IL-6）、白细胞介素-1β（IL-β）、肿瘤坏死因子-α（TNF-α）表达显著升高（P<0.01），胃组织PI3K、磷酸化蛋白激酶B（p-AKT）蛋白表达显著降低（P<0.01）；与模型组比较，给药组大鼠胃损伤明显减轻，IL-6、IL-β、TNF-α表达显著下调（P<0.01），PI3K、p-AKT蛋白表达显著上调（P<0.01）。结论：黄芪建中汤对GU的干预作用具有多途径、多靶点的特性，可能是通过激活PI3K/AKT信号通路来加速胃黏膜修复，并降低炎症而减轻胃损伤。 |
| English Summary: |
| To explore the mechanism of action of Huangqi Jianzhong Decoction in treating gastric ulcer(GU) through bioinformatics analysis and further validation with animal experiments.Methods:Active components and targets of Huangqi Jianzhong Decoction were collected from the Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform(TCMSP) and Swiss Target Prediction database.GU-related targets were extracted from gene(GeneCards) and drug(Drug Bank) databases.Using Cytoscape 3.7.2 software，the “active component-potential therapeutic target” network for Huangqi Jianzhong Decoction in treating GU was constructed.STRING and DAVID databases were used to obtain the protein-protein interaction(PPI) network，Gene Ontology(GO) enrichment，and Kyoto Encyclopedia of Genes and Genomes(KEGG) pathway enrichment analysis.The potential mechanisms of Huangqi Jianzhong Decoction in preventing and treating GU were further verified through molecular docking and animal experiments.Results:Huangqi Jianzhong Decoction has 131 potential targets for the treatment of GU，with core targets including phosphatidylinositol-4,5-bisphosphate 3-kinase catalytic subunit alpha(PIK3CA) and protein kinase B1(AKT1).KEGG analysis indicated that pathways such as the phosphatidylinositol 3-kinase/protein kinase B(PI3K/AKT) signaling pathway play important roles.Molecular docking suggested good binding affinity between core targets and core components.Animal experiments showed that compared with the normal group，the model group had increased ulcer index and inflammatory infiltration in gastric tissues，with significantly elevated expression of interleukin-6(IL-6)，interleukin-1β(IL-1β)，and tumor necrosis factor-alpha(TNF-α)(P<0.01)，and significantly decreased expression of PI3K and phosphorylated protein kinase B(p-AKT)(P<0.01).Compared with the model group，the treatment group showed significantly reduced gastric injury，downregulated expression of IL-6，IL-1β，and TNF-α(P<0.01)，and upregulated expression of PI3K and p-AKT(P<0.01).Conclusion:Huangqi Jianzhong Decoction exhibits multi-pathway and multi-target characteristics in its intervention effects on GU and the mechanism may be achieved through accelerating gastric mucosal repair and reducing gastric injury by activating the PI3K/AKT signaling pathway and lowering inflammation. |
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