益气化瘀解毒方通过调控巨噬细胞极化治疗胃癌的网络药理学分析及实验验证

Network Pharmacology Analysis and Experimental Verification of Yiqi Huayu Jiedu Decoction on Gastric Cancer through Macrophage Polarization

  • 摘要:
    目的 通过网络药理学技术及实验验证,分析益气化瘀解毒方(YHJD)治疗胃癌的活性成分及分子机制。
    方法 通过网络药理学构建中药活性成分-靶基因的交互网络,利用DAVID数据库对靶基因进行功能富集分析。采用Autodock vina进行主要成分与靶蛋白的分子对接预测。在转录水平及单细胞水平分析核心基因在胃癌中的作用机制,并通过体内实验进行验证。
    结果 筛选出YHJD与胃癌相关的176个共同靶点。功能富集分析显示,AKT1在所有通路中均显著表达,并影响胃癌预后。分子对接分析显示活性成分与靶蛋白具有良好的结合能力。在转录水平及单细胞水平的分析发现,核心基因与巨噬细胞浸润显著相关。动物实验表明,YHJD能够下调AKT1表达并促进巨噬细胞M1型极化,从而抑制胃癌进展。
    结论 益气化瘀解毒方通过多成分、多靶点机制,调控M1型巨噬细胞极化,从而抑制胃癌的进展。

     

    Abstract:
    OBJECTIVE To analyze the active components and molecular mechanisms of Yiqi Huayu Jiedu decoction (YHJD) in the treatment of gastric cancer through network pharmacology technology and experimental verification.
    METHODS The TCM active components-target genes interaction network was constructed through network pharmacology. DAVID database was used for functional enrichment analysis of target genes. Autodock vina was used for molecular docking prediction of major components and target proteins. The mechanism of action of core genes in gastric cancer was analyzed at the transcriptional level and single-cell level, and verified experimentally in vivo.
    RESULTS A total of 176 common targets between YHJD and gastric cancer were screened out. Functional enrichment analysis showed that AKT1 was significantly expressed in all pathways and affected the prognosis of gastric cancer. The active components and target proteins had good binding ability in molecular docking. Analysis of the transcription level and single cell level found that the core genes were significantly associated with macrophage infiltration. Animal experiments showed that YHJD could down-regulate AKT1 expression and promote M1 polarization of macrophages, thereby inhibiting the progression of gastric cancer.
    CONCLUSION YHJD inhibited the progression of gastric cancer by regulating the polarization of M1 macrophages through multiple components and targets.

     

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