目的 通过网络药理学、分子对接技术及动物实验探究制萎扶胃丸干预胃癌前病变 （PLGC） 的潜在作用机制。方法 通过中药系统药理学数据库与分析平台 （TCMSP） 及相关文献筛选制萎扶胃丸活性成分及对应靶点，利用 GeneCards 数据库筛选胃癌前病变疾病靶点，二者的交集靶点即为制萎扶胃丸治疗胃癌前病变的潜在作用靶点；使用 Cytoscape 软件构建“药物-活性成分-靶点”网络，STRING 数据库构建蛋白质相互作用网络，然后筛选关键活性成分和关键靶点；使用 DAVID 数据库对交集靶点进行基因本体 （GO） 和基因组百科全书（KEGG） 富集分析；采用 AutoDockTools 软件对关键活性成分和关键靶点进行分子对接验证。通过 N-甲基-N'-硝基-N-亚硝基胍 （MNNG） 为主的五因素复合法进行胃癌前病变大鼠模型复制，采用 HE 染色法检测胃组织病理学变化，Western Blot 法检测胃组织 PI3K、AKT、TNF-α、IL-6、Caspase-3 蛋白表达。结果 共获得制萎扶胃丸活性成分 258 种及对应靶点 325 个，疾病靶点 1 294 个，二者交集靶点 （潜在作用靶点） 139 个。筛选出关键活性成分槲皮素、木犀草素、山柰酚、β-谷甾醇等，关键靶点 AKT1、CASP3、IL-6、TNF 等。分析得到GO 相关条目 950 条，KEGG 相关通路 177 条，主要涉及 PI3K/AKT、MAPK、IL-17、TNF 及细胞凋亡等通路。分子对接显示，槲皮素、木犀草素、山柰酚、β-谷甾醇与 AKT1、TP53、CASP3、IL-6、TNF 等度值前 10 位关键靶点具有较好结合活性和稳定性。动物实验验证结果显示，与模型组比较，制萎扶胃丸组大鼠胃组织病理形态得到明显改善；同时该组大鼠胃组织中 PI3K、p-PI3K、AKT、p-AKT、TNF-α、IL-6 蛋白表达水平明显降低 （P＜0.05，P＜0.01） ，Caspase-3 蛋白表达明显升高 （P＜0.01） 。结论 制萎扶胃丸治疗胃癌前病变具有多成分、多靶点、多途径的特征，能够通过抑制炎症反应、促进细胞凋亡发挥干预作用，可能与调控 PI3K/AKT信号通路有关。

Objective To explore the potential mechanism of Zhiwei Fuwei Pill in intervening precancerous lesions of gastric cancer（PLGC）by network pharmacology，molecular docking technology and animal experiments. Methods The active components and corresponding targets of Zhiwei Fuwei Pill were screened by traditional Chinese medicine database and analysis platform （TCMSP） and related literature，and the disease targets of PLGC were screened by GeneCards database. The intersection target of the two targets was the potential target of Zhiwei Fuwei Pill in the treatment of PLGC. Cytoscape software was used to construct the“drug-active ingredients-targets”network，and STRING database was applied to establish the protein interaction network，and then the key active ingredients and key targets were screened. Gene Ontology （GO） and Kyoto Encyclopedia of Genes and Genomes （KEGG） enrichment analysis were performed on the intersection targets using the DAVID database. AutoDockTools software was used to verify the molecular docking of key active ingredients and key targets. PLGC model was replicated by N-methyl-N'-nitro-N-nitrosoguanidine（MNNG）and other comprehensive factors. HE staining was used to detect the pathological changes of gastric tissue. Western Blot was used to detect the protein expression of PI3K，AKT，TNF-α，IL-6 and Caspase-3 in gastric tissue. Results A total of 258 active components，325 corresponding targets，1 294 disease targets and 139 intersection targets （potential targets） of Zhiwei Fuwei Pill were obtained. The key active ingredients were quercetin，luteolin，kaempferol，beta-sitosterol，etc. The key targets were AKT1，CASP3，IL-6，TNF，etc. There were 950 GO-related items and 177 KEGG-related pathways，mainly involving PI3K/AKT，MAPK，IL-17，TNF and apoptosis. Molecular docking showed that good binding activity and stability between quercetin，luteolin，kaempferol，and beta-sitosterol and the top 10 key targets in terms of degree value（AKT1，TP53，CASP3，IL-6 and TNF， etc.） were found. The results of animal experiments showed that compared with the model group， the pathological morphology of gastric tissue in rats of Zhiwei Fuwei Pill group was significantly improved. Simultaneously，the expression levels of PI3K，p-PI3K，AKT，p-AKT，TNF-α and IL-6 in gastric tissue of rats in this group were significantly decreased （P＜0.05，P＜0.01），and the expression of Caspase-3 protein was significantly increased（P＜0.01）. Conclusion Zhiwei Fuwei Pill has the characteristics of multi-components，multi-targets and multi-pathways in the treatment of PLGC. It can play an intervention role by inhibiting inflammatory response and promoting apoptosis，which may be related to the regulation of PI3K/AKT signaling pathway.

R285.5

国家自然科学基金项目（82060860）；甘肃省自然科学基金项目（21JR7RA588）；2023年度甘肃中医药大学（博士）研究生创新基金项目