扶正通络解毒方对慢性萎缩性胃炎“炎-癌”转化小鼠的作用及机制研究  

Study on the Effect and Mechanism of Fuzheng Tongluo Jiedu Prescription on“Inflammation-Cancer”Transformed Mice of Chronic Atrophic Gastritis

作　　者：杨泽虹 麦紫涵 陈彦彤 江晓涛 安金琪 阮舒琪 曾颖凤 文艺[1,2] 刘凤斌 李培武[1,2] YANG Zehong;MAI Zihan;CHEN Yantong;JIANG Xiaotao;AN Jinqi;RUAN Shuqi;ZENG Yingfeng;WEN Yi;LIU Fengbin;LI Peiwu(The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;Guangdong Clinical Research Institute of Traditional Chinese Medicine,Guangzhou 510405 Guangdong,China;Postdoctoral Mobile Station,Guangzhou University of Chinese Medicine,Postdoctoral Research Mobile Station,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;The First Clinical Medical School,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;School of Continuing Education,Guangzhou University of Chinese Medicine,Guangzhou 510405 Guangdong,China;Meizhou Traditional Chinese Medicine Hospital,Meizhou 514500 Guangdong,China;Baiyun Hospital of The First Affiliated Hospital of Guangzhou University of Chinese Medicine,Guangzhou 510470 Guangdong,China)

机构地区：[1]广州中医药大学第一附属医院,广东广州510405 [2]广东省中医临床研究院,广东广州510405 [3]广州中医药大学博士后科研流动站,广东广州510405 [4]广州中医药大学第一临床医学院,广东广州510405 [5]广州中医药大学继续教育学院,广东广州510405 [6]梅州市中医医院,广东梅州514500 [7]广州中医药大学第一附属医院白云医院,广东广州510470

出　　处：《中药新药与临床药理》2025年第3期338-348,共11页Traditional Chinese Drug Research and Clinical Pharmacology

基　　金：国家自然科学基金项目(82474404,82474408,82104602);广东省自然科学基金面上项目(2023A1515011019,2024A1515012532);国家中医药传承创新中心科研专项(2022ZD01);广州中医药大学中医学学科中医基础理论研究“揭榜挂帅”项目(2022JB04);广州市科技计划项目市校(院)企联合项目(2024A03J0408);广州中医药大学“双一流”与高水平大学学科后备人才培育项目;广东省中医药局中医药科研平台专项(青年项目)。

摘　　要：目的探讨扶正通络解毒方(FTJF)干预慢性萎缩性胃炎(CAG)“炎-癌”转化的作用机制。方法(1)通过检索TCMSP、HERB及Swiss Target Prediction数据库,筛选出FTJF方中各中药的活性成分及其作用靶点;通过GeneCards、OMIM、Drugbank、TTD和DisDeNet数据库检索、筛选获得CAG“炎-癌”转化相关疾病靶点;使用Venny 2.1在线平台对FTJF活性成分作用靶点与CAG“炎-癌”转化疾病靶点取交集,获得FTJF干预CAG“炎-癌”转化的潜在作用靶点。通过Cytoscape 3.9.1软件构建“药物-活性成分-靶点”网络,并筛选出核心活性成分;通过STRING数据库进行潜在作用靶点蛋白互作(PPI)网络分析,筛选核心靶点;通过DAVID数据库对潜在作用靶点进行基因本体(GO)功能及京都基因与基因组百科全书(KEGG)通路富集分析。(2)采用N-甲基-N-亚硝基脲(MNU)化学诱导法复制CAG“炎-癌”转化小鼠模型。将C57BL/6小鼠随机分为空白组、模型组及FTJF低、中、高剂量组(生药量9.56、19.11、38.22 g·kg^(-1)),每组10只,灌胃给药,每日1次,持续8周。采用苏木精-伊红(HE)染色法及阿利新蓝/过碘酸雪夫(AB/PAS)染色法观察胃黏膜组织病理变化;ELISA法检测血清胃功能激素胃蛋白酶原Ⅰ(PGⅠ)、胃蛋白酶原Ⅱ(PGⅡ)、胃泌素17(G-17)和炎性因子白细胞介素6(IL-6)、肿瘤坏死因子α(TNF-α)、白细胞介素1β(L-1β)的水平;q-PCR法检测胃黏膜组织肿瘤蛋白p53(TP53)、髓细胞增生原癌基因(MYC)、表皮生长因子受体(EGFR)基因表达水平。结果(1)共筛选得到199种活性成分,795个作用靶点,2074个疾病相关靶点,FTJF干预CAG“炎-癌”转化的307个潜在作用靶点。分析得到槲皮素、芹菜素、木犀草素、熊果酸等核心活性成分;TP53、AKT1、GAPDH、MYC、EGFR、VEGFA、TNF、JUN、CASP3、INS等核心靶点;KEGG通路富集分析主要涉及癌症通路、乙型肝炎、PI3K/Akt信号通路等。(2)与空白组比较,模型组小鼠胃黏膜�Objective To explore the mechanism of Fuzheng Tongluo Jiedu Prescription(FTJF)on the“inflammationcancer”transformation of chronic atrophic gastritis(CAG).Methods(1)The active components of each Chinese medicinal in FTJF and their corresponding targets were screened out by searching TCMSP,HERB and Swiss Target Prediction databases.GeneCards,OMIM,Drugbank,TTD and DisDeNet databases were used to search and screen for CAG“inflammation-cancer”transformation-related disease targets.Venny 2.1 was used to intersect the target of FTJF active ingredients with the target of CAG“inflammation-cancer”transformation disease,and the potential target of FTJF intervention in CAG“inflammation-cancer”transformation was obtained.The“drugs-active ingredients-targets”network was constructed by Cytoscape 3.9.1 software,and the core active ingredients were screened out.The potential target protein-protein interaction(PPI)network was analyzed by STRING database to screen the core targets.Gene ontology(GO)function and Kyoto Encyclopedia of Genes and Genomes(KEGG)pathway enrichment analysis of nuclear potential targets were performed by DAVID database.(2)N-methyl-N-nitrosourea(MNU)chemical induction method was used to replicate the“inflammation-cancer”transformed mouse model of CAG.C57 BL/6 mice were randomly divided into blank group,model group and FTJF low-,medium-and high-dose groups(crude drug 9.56,19.11,38.22 g·kg^(-1)),with 10 mice in each group and were all given intragastric administration once a day for 8 consecutive weeks.Hematoxylin-eosin(HE)staining and alcian blue/periodic acid Schiff(AB/PAS)staining were used to observe the pathological changes of gastric mucosa.The levels of serum gastric function hormones pepsinogen Ⅰ(PGⅠ),pepsinogen Ⅱ(PGⅡ),gastrin 17(G-17)and inflammatory factors interleukin 6(IL-6),tumor necrosis factor α(TNF-α)and interleukin 1β(L-1β)were detected by ELISA.The expression levels of tumor protein p53(TP53),myeloproliferative oncogene(MYC)and epidermal growth factor recep

关 键 词：扶正通络解毒方 慢性萎缩性胃炎 “炎-癌”转化 胃功能激素 炎症反应 癌症通路 小鼠 

分 类 号：R285.5[医药卫生—中药学]