【摘要】 目的：探究化瘀解毒方对慢性萎缩性胃炎（chronic atrophic gastritis, CAG）大鼠的保护作用及分子机制。方法：采用N-甲基-N’-硝基-N-亚硝基胍（N-methyl-N’-nitro-N-nitrosoguanidine, MNNG）自由饮等综合因素法建立CAG大鼠模型。造模成功后，将大鼠随机分为模型组、胃复春（Weifuchun, WFC）对照组及低、中、高剂量化瘀解毒方组。监测各组大鼠体重、评估胃黏膜状态、检测血清炎症因子水平及胃功能指标。体外构建GES-1恶性转化细胞（malignantly transformed GES-1 cells, MC）模型，采用CCK8法、细胞划痕和Transwell侵袭实验检测BCHR含药血清对MC增殖、迁移和侵袭能力的影响。整合网络药理学预测、分子对接模拟、Western blot和免疫组织化学分析，筛选并验证干预CAG的关键靶点；通过siRNA敲减关键靶点Bcl-2相关转录因子1(Bcl-2-associated transcription factor 1, BTF)或缺氧诱导因子1α(hypoxia-inducible factor-1α, HIF-1α)，探究其在CAG中的调控作用。结果：化瘀解毒方干预可显著逆转CAG大鼠体重下降、胃黏膜病理损伤及血清炎症因子和胃功能指标的异常。20%化瘀解毒方含药血清可显著抑制MC细胞增殖、迁移与侵袭能力。网络药理学分析与实验验证结果表明：BTF和HIF-1α是化瘀解毒方干预CAG的关键靶点，化瘀解毒方可显著下调其蛋白表达；敲减BTF或HIF-1α均可下调HIF-1α下游靶基因血管内皮生长因子（vascular endothelial growth factor A, VEGFA）和促红细胞生成素（eryropoietin, EPO）的mRNA表达。结论：化瘀解毒方可有效改善CAG，其保护作用与抑制BTF/HIF-1α信号通路有关。更多还原

【Abstract】 AIM: To investigate the protective effect of Huayu-Jiedu formula(BCHR) on rats with chronic atrophic gastritis(CAG) and the molecular mechanisms involved. METHODS: A rat model of CAG was established by using the comprehensive factor method and giving the rats unrestricted access to water containing N-methyl-N’-nitro-N-nitrosoguanidine(MNNG). After establishing the model, the rats were randomly divided into five groups: a model group; a Weifuchun(WFC) control group; and low-, medium-, and high-dose BCHR groups. Body weight, gastric mucosa status, serum inflammatory factor levels, and gastric function indicators were monitored. An in-vitro model of malignantly transformed GES-1 cells(MCs) was also constructed. The effects of BCHR-containing serum on MC proliferation, migration, and invasion were detected using a CCK8 assay, cell scratch assay, and Transwell invasion assay. Network pharmacology prediction, molecular docking simulation, Western blot, and immunohistochemistry(IHC) analyses were performed to screen and verify key targets for CAG intervention. Small interfering RNA(siRNA) was used to knock down key targets BTF or HIF-1α and explore their regulatory roles in CAG. RESULTS: The BCHR intervention significantly reversed weight loss, gastric mucosal pathological damage, and abnormalities of serum inflammatory factors and gastric function indicators in CAG rats. Serum containing 20% BCHR significantly inhibited MC proliferation, migration, and invasion. Network pharmacology analysis and experimental verification showed that BTF and HIF-1α were key targets of BCHR in the CAG intervention, and BCHR significantly downregulated their protein expression. Knocking down BTF and HIF-1α both reduced the mRNA expression of HIF-1α downstream target genes VEGFA and EPO. CONCLUSION: The BCHR can effectively improve CAG, and its protective effect is associated with inhibition of the BTF/HIF-1α signaling pathway.更多还原