基于网络药理学及体外实验方法探究和验证理中丸治疗慢性萎缩性胃炎的作用机制  

Explore and verify the mechanism of action of Lizhong Wan in treatment of chronic atrophic gastritis based on network pharmacology and in vitro experimental method

作　　者：汪燕 张展浩 王佳慧 郑洋 赵铁建 WANG Yan;ZHANG Zhanhao;WANG Jiahui;ZHENG Yang;ZHAO Tiejian(Department of Spleen and Stomach Diseases,Hangzhou Hospital of Traditional Chinese Medicine,Hangzhou 310007,Zhejiang,China;School of Basic Medicine,Guangxi University of Chinese Medicine,Nanning 530200,Guangxi,China)

机构地区：[1]杭州市中医院脾胃病科,浙江杭州310007 [2]广西中医药大学基础医学院,广西南宁530200

出　　处：《中国现代医生》2024年第34期68-76,83,共10页China Modern Doctor

摘　　要：目的运用网络药理学及体外实验方法探究并验证理中丸治疗慢性萎缩性胃炎(chronic atrophic gastritis,CAG)的分子机制。方法借助中药系统药理学数据库和分析平台筛选理中丸的有效活性成分,并通过PubChem、Swiss Target Prediction数据库获取理中丸的相关作用靶点。借助GeneCards、OMIM和DisGeNET数据库获取CAG的相关靶点。利用Venn工具获得理中丸治疗CAG的药物-疾病共同靶点,借助STRING数据库构建理中丸治疗CAG的药物-疾病共同靶点互作网络。应用Cytoscape软件构建理中丸治疗CAG的“药物-疾病-靶点-通路”网络,对理中丸治疗CAG的药物-疾病共同靶点进行基因功能和通路富集分析。运用Moe软件对药物活性成分与关键靶点进行分子对接和结合能力预测。构建脾胃虚寒型CAG大鼠模型,观察理中丸对大鼠胃组织形态改变、胃黏膜细胞凋亡及CAG关键靶点信使RNA(messenger RNA,mRNA)和蛋白水平表达的影响。结果共筛选出理中丸有效活性成分57种,包括花生四烯酸、人参皂苷Rg5、五味子酯乙、阿朴天仙子碱和人参皂苷Rh2等;获得理中丸相关作用靶点869个。获得理中丸与CAG的共同靶点47个,其中关键靶点包括肿瘤蛋白P53(tumor protein P53,TP53)、白细胞介素-6(interleukin-6,IL-6)、肿瘤坏死因子-α(tumor necrosis factor-α,TNF-α)、表皮生长因子受体(epidermal growth factor receptor,EGFR)、B细胞淋巴瘤2(B-cell lymphoma 2,Bcl-2)等。通路富集分析共获得135条通路,主要包括肿瘤的发病途径、肿瘤中的蛋白聚糖、胆碱能突触、磷脂酰肌醇3激酶/蛋白激酶B信号通路等。分子对接结果显示,TP53、IL-6、TNF-α、EGFR、Bcl-2与五味子酯乙和人参皂苷Rh2有较好的结合活性。体外实验发现,模型组大鼠的脾胃虚寒证候评分显著高于空白组;理中丸可改善CAG大鼠的病理变化,显著减少胃黏膜细胞凋亡,降低胃黏膜组织中TP53、IL-6、TNF-α、EGFR、Bcl-2 mObjective To investigate the molecular mechanism of Lizhong Wan in treatment of chronic atrophic gastritis(CAG)using network pharmacology and in vitro experimental method.Methods The active ingredients of Lizhong Wan were screened by Traditional Chinese Medicine Systems Pharmacology Database and Analysis Platform,and the related targets were obtained from PubChem and Swiss Target Prediction databases.The CAG-related targets were obtained from GeneCards,OMIM and DisGeNET databases.The drug-disease common targets of Lizhong Wan and CAG were obtained by Venn tool.The interaction network of common targets of Lizhong Wan and CAG was constructed with the help of STRING database,and the drug-disease-target-pathway network was constructed with the help of Cytoscape software.Gene function and pathway enrichment analyses were performed on the common targets.The molecular docking and binding ability of the active ingredients of the drug and the key targets were predicted by using Moe software.The mice of spleen and stomach deficiency cold syndrome CAG was established.The effects of Lizhong Wan on the morphological changes of gastric tissue,apoptosis of gastric mucosa cells and the expression of messenger RNA(mRNA)and protein of the key target of CAG were observed.Results A total of 57 active ingredients of Lizhong Wan were screened,including arachidonic acid,ginsenoside Rg5,gomisin B,aposiopolamine and ginsenoside Rh2.869 active targets of Lizhong Wan were obtained.CAG and Lizhong Wan had 47 common targets,the key common targets including tumor protein P53(TP53),interleukin-6(IL-6),tumor necrosis factor-α(TNF-α),epidermal growth factor receptor(EGFR),B-cell lymphoma 2(Bcl-2),etc..A total of 135 pathways were obtained by enrichment analysis,mainly including tumor pathogenesis,proteoglycan in tumor,cholinergic synapse,phosphoinositide 3-kinase/protein kinase B signaling pathway,etc..Molecular docking results showed that TP53,IL-6,TNF-α,EGFR,Bcl-2 had good binding activity with gomisin B and ginsenoside Rh2.Meanwhile,in vit

关 键 词：理中丸 慢性萎缩性胃炎 网络药理学 体外实验 细胞凋亡 

分 类 号：R285.5[医药卫生—中药学]