目的 基于网络药理学研究黄芪-三七-白花蛇舌草（HSB）对慢性萎缩性胃炎（CAG）大鼠的治疗作用。方法 根据中药系统药理学数据库与分析平台（TCMSP）、Uniprot、GeneCards、NCBI、DisGeNET和OMIM等数据库筛选HSB主要成分靶点和CAG相关靶点并绘制韦恩图。利用STRING数据库和Cytoscape 3.8.0软件绘制蛋白质-蛋白质相互作用（PPI）网络图。构建“药物-成分-靶点-疾病”网络，并进行拓扑分析，筛选出核心成分。并用DAVID数据库对关键交集靶点进行基因本体（GO）注释及京都基因与基因组百科全书（KEGG）通路富集分析。运用苏木精-伊红（HE）染色、ELISA法、实时荧光定量PCR法（qRT-PCR）检测和Western blotting检测验证HSB对CAG大鼠的治疗作用。结果 筛选出槲皮素、山柰酚、β-谷甾醇、异鼠李素和芒柄花素等31个活性成分。PPI网络中关键交集靶点有42个，其中核心靶点有蛋白激酶B抗体1（AKT1）、白细胞介素6（IL6）、环加氧酶2（PTGS2）、半胱氨酸天冬氨酸蛋白酶3（CASP3）、过氧化物酶体增殖物激活受体γ （PPARG）和基质金属蛋白酶9（MMP9）等。GO富集分析共得到生物过程（BP） 1 576条、分子功能（MF） 56条和细胞成分（CC） 13条。KEGG通路富集分析得到145条信号通路，其中与CAG治疗相关的通路有PI3K-Akt signalingpathway、Apoptosis和肿瘤坏死因子（TNF） signaling pathway等。动物实验证实HSB不但改善CAG大鼠的胃黏膜组织的病理形态；还能升高CAG大鼠血清中胃蛋白酶原（PG） Ⅰ、TNF-α、白细胞介素（IL）-6的水平和PG I/PG Ⅱ比率，降低CAG大鼠血清中PG Ⅱ水平；同时其还可以抑制CAG大鼠PI3K/Akt信号通路的激活和Bcl-2的表达。结论 通过网络药理学和动物实验验证，发现HSB可通过改善胃黏膜的分泌功能、减轻CAG的炎症反应、抑制PI3K-Akt信号通路的激活和降低Bcl-2的表达等对CAG起到防治作用。

Objective To investigate the therapeutic effect of Astragali Radix-Notoginseng Radix et Rhizoma-Hedyoti Diffusae Herba (HSB) on chronic atrophic gastritis (CAG) in rats based on network pharmacology. Methods Active components and targets of HSB, as well as CAG-related targets, were screened from databases such as Traditional Chinese Medicine Systems Pharmacology (TCMSP), UniProt, GeneCards, NCBI, DisGeNET, and OMIM, followed by the construction of Venn diagrams. A protein-protein interaction (PPI) network was generated using the STRING database and visualized with Cytoscape 3.8.0. A “drug-component-target-disease” network was built, and topological analysis was performed to identify core components. Key intersection targets were subjected to GO and KEGG enrichment analysis using the DAVID database. The therapeutic effect of HSB on CAG rats was validated through HE staining, ELISA, qRT-PCR, and Western blotting. Results A total of 31 active components were screened, including quercetin, kaempferol, beta-sitosterol, isorhamnetin, and formononetin. The PPI network revealed 42 key intersection targets, with core targets such as AKT1, IL6, PTGS2, CASP3, PPARG, and MMP9. GO enrichment analysis yielded 1 576 biological process (BP) terms, 56 molecular function (MF) terms, and 13 cellular component (CC) terms. KEGG pathway analysis identified 145 signaling pathways, including the PI3K-Akt signaling pathway, Apoptosis, and TNF signaling pathway, which are closely related to CAG treatment. Animal experiments demonstrated that HSB not only improved the pathological morphology of gastric mucosal tissues in CAG rats but also increased serum levels of PG I, TNF-α, IL-6, and the PG I/PG II ratio, while decreasing PG II levels. Additionally, HSB inhibited the activation of the PI3K/Akt signaling pathway and the expression of Bcl-2 in CAG rats. Conclusion Through network pharmacology and animal experimental validation, HSB was found to prevent and treat CAG by improving gastric mucosal secretory function, alleviating inflammatory responses, inhibiting the activation of the PI3K-Akt signaling pathway, and reducing Bcl-2 expression.

R965

深圳市龙岗区经济与科技发展专项资金医疗卫生科技计划项目（LGWJ2021-75）