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，2 074 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，模型组小鼠胃黏膜结构严重破坏，细胞排列紊乱，可见大量炎性细胞 浸润，细胞明显空泡样变，腺腔形成大小不等的黏液湖，有分泌酸性黏液的肠化生腺体形成；部分黏膜呈锯齿 样或 U 型管样，两个或多个腺腔单层上皮变为多层无规则排列、无管腔结构的细胞团，表现出组织异型性；血 清 PGⅠ水平显著降低（P＜0.001），PGⅡ、G-17、IL-6、TNF-α、IL-1β 水平均显著升高（P＜0.001）；胃黏膜 组织 TP53 mRNA 表达显著下调（P＜0.001），MYC、EGFR mRNA 表达显著上调（P＜0.05，P＜0.01）。与模型 组比较，FTJF 各剂量组小鼠胃黏膜组织细胞形态异常情况均有所好转，炎性浸润区域减少，空泡样变、黏液 湖及组织异型性减少；血清 PGI 水平显著升高（P＜0.05，P＜0.001），PGⅡ、IL-6、TNF-α 水平均显著降低 （P＜0.05，P＜0.01，P＜0.001）；胃黏膜组织 TP53 mRNA 表达显著上调（P＜0.05，P＜0.01），MYC、EGFR mRNA 表达显著下调（P＜0.05，P＜0.01）。FTJF 中、高剂量组的血清 G-17、IL-1β 水平显著降低（P＜0.05，P＜0.01，P＜0.001）。结论 FTJF 可能通过槲皮素、芹菜素等多种活性成分，调节胃功能激素分泌水平、减轻 炎症反应、下调癌症信号通路，发挥干预 CAG “炎-癌”转化的作用。

Objective To explore the mechanism of Fuzheng Tongluo Jiedu Prescription（FTJF） on the “inflammation- cancer” 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 receptor （EGFR） genes in gastric mucosa were detected by q-PCR. Results （1） A total of 199 active ingredients，795 targets，2 074 disease-related targets，and 307 potential targets of FTJF intervention in “inflammation-cancer” transformation of CAG were screened. The core active ingredients such as quercetin，apigenin，luteolin and ursolic acid were analyzed. TP53，AKT1， GAPDH，MYC，EGFR，VEGFA，TNF，JUN，CASP3，INS and other core targets；KEGG pathway enrichment analysis mainly involved cancer pathway，hepatitis B，PI3K/Akt signaling pathway，etc. （2） Compared with the blank group，the gastric mucosal structure of the model group was seriously damaged，the cell arrangement was disordered，a large number of inflammatory cells were infiltrated，the cells were obviously vacuolated，the glandular cavity formed a mucus lake of different sizes，and the intestinal metaplasia glands secreting acidic mucus were formed. Part of the mucosa was serrated or U-shaped tube-like，two or more glandular cavity single-layer epithelium became multilayer irregular arrangement，no lumen structure of the cell mass，showing tissue atypia. The levels of serum PGI were significantly decreased（P＜0.001） ，and the levels of PGII，G-17，IL-6，TNF-α and IL-1β were significantly increased （P＜0.001） . The mRNA expression of TP53 in gastric mucosa was significantly down-regulated （P＜ 0.001）， and the mRNA expressions of MYC and EGFR was significantly up-regulated （P＜0.05， P＜0.01） . Compared with the model group，the morphological abnormalities of gastric mucosal cells in each FTJF dose group were improved，the inflammatory infiltration area was reduced，vacuolar degeneration，mucus lake and tissue atypia were reduced；the levels of serum PGI were significantly increased （P＜0.05，P＜0.001） ，and the levels of PGII，IL-6 and TNF-α were significantly decreased （P＜0.05，P＜0.01，P＜0.001） . The mRNA expression of TP53 in gastric mucosa was significantly up-regulated （P＜0.05，P＜0.01），and the mRNA expressions of MYC and EGFR were significantly down-regulated （P＜0.05，P＜0.01） . The levels of serum G-17 and IL-1β in the medium- and high- dose groups of FTJF were significantly decreased （P＜0.05，P＜0.01，P＜0.001） . Conclusion FTJF may regulate the secretion level of gastric functional hormones， reduce the inflammatory response， down-regulate the cancer signaling pathway，and play a role in interfering with the transformation of CAG “inflammation-cancer” through various active ingredients such as quercetin and apigenin.

R285.5

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）