目的 基于网络药理学和肠道菌群探讨加味七方胃痛颗粒抗慢性萎缩性胃炎（CAG）的作用机制。方法 采用多因素复合造模法构建CAG大鼠模型，随机分为对照组、模型组、胃复春组及加味七方胃痛颗粒组。给药后检测各组大鼠体质量、胃组织病理形态，检测其血清肿瘤坏死因子α（TNF-α）、白细胞介素6（IL-6）、IL-1β水平，通过16S rRNA测序法检测各组大鼠肠道菌群变化；采用网络药理学方法，筛选加味七方胃痛颗粒调控肠道菌群治疗CAG的关键靶点与主要有效成分；采用蛋白免疫印迹法（Western blotting）验证京都基因与基因组百科全书（KEGG）富集关键靶点相关蛋白表达。结果 与模型组比较，加味七方胃痛颗粒组大鼠体质量回升，胃黏膜组织病变改善，血清TNF-α、IL-6、IL-1β水平降低。菌群测序结果显示，主坐标分析（PCoA）中4组大鼠肠道菌群结构存在显著差异。模型组菌群偏离正常状态，加味七方胃痛颗粒可使其向对照组恢复。模型组多个菌群分类单元丰度出现异常改变，药物干预后菌群丰度得到有效纠正。网络药理学分析得到药物-疾病-肠道菌群的交集靶点131个，基因本体（GO）富集分析共得到521个相关条目，其中生物过程（BP） 402条，细胞组成（CC） 34条，分子功能（MF） 85条。KEGG富集共得到158条信号通路。网络药理学结果表明，加味七方胃痛颗粒调控肠道菌群抗CAG的作用机制与炎症反应有关。Western blotting结果显示，加味七方胃痛颗粒下调Janus蛋白酪氨酸激酶2（JAK2）、信号转导和转录激活因子3（STAT3）表达。结论 加味七方胃痛颗粒抗CAG的作用可能与调控STAT3、JAK2、IL-6、IL-1β、TNF-α等炎症靶点及改善肠道菌群环境有关，其机制可能涉及JAK2/STAT3信号通路，可为加味七方胃痛颗粒深入研究提供方向。

Objective To investigate the mechanism of Modified Qifang Weitong Granules against chronic atrophic gastritis (CAG) based on network pharmacology and gut microbiota. Methods A CAG rat model was established by multi-factor composite modeling, and the rats were randomly divided into model group, Weifuchun group, Modified Qifang Weitong Granules group, and blank control group. After drug administration, body weight and gastric histopathological morphology were examined, and serum levels of tumor necrosis factor-α (TNF-α), interleukin-6 (IL-6), and interleukin-1β (IL-1β) were measured. Changes in gut microbiota were assessed by 16S rRNA sequencing. Network pharmacology was used to screen key targets and major active components of Modified Qifang Weitong Granules in regulating gut microbiota for CAG treatment. Western blotting was performed to verify the expression of proteins related to key targets identified by KEGG enrichment. Results Compared with the model group, the Modified Qifang Weitong Granules group showed increased body weight, improved gastric mucosal lesions, and decreased serum levels of TNF-α, IL-6, and IL-1β. Microbiome sequencing revealed that principal coordinate analysis (PCoA) and non-metric multidimensional scaling (NMDS) displayed significant differences in gut microbiota structure among the four groups. The microbiota in the model group deviated from the normal state, while Modified Qifang Weitong Granules could shift it towards the control group. Abundance of multiple microbial taxa was abnormally altered in the model group and was effectively corrected after drug intervention. Network pharmacology identified 131 intersecting targets among drug, disease, and gut microbiota. GO functional enrichment analysis yielded 521 terms, including 402 biological processes (BP), 34 cellular components (CC), and 85 molecular functions (MF). KEGG enrichment revealed 158 signaling pathways. Network pharmacology results indicated that the anti-CAG mechanism of Modified Qifang Weitong Granules is related to inflammatory responses. Western blotting demonstrated that Modified Qifang Weitong Granules downregulated the expression of JAK2 and STAT3. Conclusions The anti-CAG effect of Modified Qifang Weitong Granules may be associated with regulating inflammatory targets such as STAT3, JAK2, IL-6, IL-1β, and TNF-α, as well as improving the gut microbiota environment. Its mechanism may involve the JAK2/STAT3 signaling pathway, which could provide directions for further research on Modified Qifang Weitong Granules.

R285.5

国家自然科学地区基金项目（82360959）；广西自然科学基金重点项目（2024GXNSFDA010021）；广西自然科学基金青年科学基金（2024GXNSFBA010160）