中医学报2025，Vol.40Issue(6)：1302-1310,9.DOI:10.16368/j.issn.1674-8999.2025.06.210
枳术丸调控PI3K/AKT/NF-κB信号通路治疗慢性萎缩性胃炎的作用机制研究
Mechanism of Zhizhu Pill Regulating PI3K/AKT/NF-κB Signaling Pathway in Treatment of Chronic Atrophic Gastritis
摘要
Abstract
Objective:Based on phosphatidylinositol 3-kinase/protein kinase B/nuclear factor-κB(phosphatidylinositol-3-kinase/protein kinase B/nuclear factor kappa-B,PI3K/AKT/NF-κB)Exploring the mechanism of action of Zhizhu Pill in treating chronic atrophic gastritis(CAG)through signal pathway analysis.Method:Retrieve the active ingredients and targets of Zhizhu Pill(Zhishi,Baizhu)from the TCMSP database,and use GeneCards,OMIM,DisGeNET,and DrugBank databases to search for CAG targets.Using Venny 2.1.0 software,the intersection targets of Zhizhu Wan and CAG were obtained and uploaded to STRING 12.0 database to con-struct a protein-protein interaction(PPI)network and screen for core targets.Perform Kyoto Encyclopedia of Genes and Genomes(KEGG)enrichment analysis using Metascape database.RAW264.7 cells were treated with 2 mg·L-1 LPS to induce an inflammatory model.Zhizhu Pill(150,200,300,400 mg·L-1)was used for intervention,and blank group(Control)and model group(LPS)were set up.The Griess method was used to determine the content of nitric oxide(NO),and the ELISA method was used to detect the con-tent of tumor necrosis factor-α(TNF-α),interleukin-6(IL-6),and IL-1 β.52 SD rats were randomly divided into a normal group(CON),a model group(CAG),a low-dose Zhizhu Wan group(ZZW-L,8.1 g·kg-1),and a high-dose Zhizhu Pill group(ZZW-H,16.2 g·kg-1),with 8 rats in each group.Except for the CON group,all other rats were used to establish CAG models by combining MNNG with ranitidine and hunger and satiety disorders.After 8 weeks of administration,HE staining was used to observe the pathological morphology of the rat antrum.ELISA was used to detect the levels of serum pepsinogen Ⅰ(PG Ⅰ),pepsinogen Ⅱ(PG Ⅱ),PG Ⅰ/PGⅡ(PGR),TNF-α,IL-6,and IL-1β.Western blot was used to detect the expression levels of PI3K/AKT/NF-κB pathway related proteins in the antrum.Result:There are 118 targets of Zhizhu Pill,662 targets of CAG,and 48 intersecting targets of the two.The core targets include protein kinase B(AKT1),tumor protein 53(TP53),B-cell lymphoma-2(BCL2),etc.The KEGG pathway includes PI3K/AKT signaling pathway,NF-κ B signaling pathway,etc.Cell experiments showed that compared with the Control group,the LPS group increased the release of NO,TNF-α,IL-6,and IL-1β levels in cells(P＜0.01);Compared with the LPS group,the Zhi Zhu Wan group showed a decrease in cellular NO release,TNF-α,IL-6,and IL-1 β levels(P＜0.05).Animal experiments showed that there were no significant abnormalities in the pathological morphology of the gastric antrum tis-sue in CON group rats;The gastric antral mucosal structure of rats in the CAG group was disrupted,accompanied by infiltration of in-flammatory cells;Compared with the CAG group,the ZZW-L and ZZW-H groups showed reduced atrophy of gastric antral glands and infiltration of inflammatory cells in rats.Compared with the CON group,the serum levels of PG Ⅱ,TNF-α,IL-6,and IL-1β in-creased in the CAG group,while the levels of PG Ⅰ and PGR decreased(P＜0.01);Compared with the CAG group,the levels of serum PG Ⅱ,TNF-α,IL-6,and IL-1β in the ZZW-L and ZZW-H groups of rats decreased(P＜0.05),while the levels of PG Ⅰ and PGR increased(P＜0.05).Compared with the CON group,the levels of p-PI3K/PI3K,p-AKT/AKT,and p-NF-κB/NF-κB in the gastric antrum of rats in the CAG group increased(P＜0.01);Compared with the CAG group,the levels of p-PI3K/PI3K,p-AKT/AKT,and p-NF-κB/NF-κB in the gastric antrum of rats in the ZZW-H group were reduced(P＜0.05).Conclusion:Zhizhu Pill may exert therapeutic effects on CAG by regulating the PI3 K/AKT/NF-κB signaling pathway,inhibiting inflammatory re-sponses.关键词
枳术丸/慢性萎缩性胃炎/PI3K/AKT/NF-κB信号通路/网络药理学/炎症反应Key words
Zhizhu Pill/chronic atrophic gastritis/PI3K/AKT/NF-κB signaling pathway/network pharmacology/inflammatory reaction分类
医药卫生引用本文复制引用
窦盈,郭辉,王智民,代丽萍,许二平..枳术丸调控PI3K/AKT/NF-κB信号通路治疗慢性萎缩性胃炎的作用机制研究[J].中医学报,2025,40(6):1302-1310,9.基金项目
河南省科技研发计划联合基金(优势学科培育类)重点项目(222301420023) （优势学科培育类）
2023年度河南省高校科技创新团队项目(23IRTSTHN028) （23IRTSTHN028）
