目的 基于蛋白激酶B（Akt）/核因子-κB（NF-κB）信号通路研究胃康胶囊对乙醇诱导的大鼠胃溃疡的保护作用，并探索其可能的作用机制。方法 SD大鼠随机分为对照组、模型组、奥美拉唑（阳性药，20 mg·kg^-1）组和胃康胶囊低、中、高剂量（480、960、1 440 mg·kg^-1）组，每组6只。除对照组外，各组大鼠单次ig 75%乙醇（10 mL·kg^-1）造模。造模1 h后各给药组ig相应药物，对照组、模型组ig等量0.5% CMC-Na溶液，每天1次，连续3 d，于第3天ig 6 h后，将大鼠麻醉，腹主动脉采血，收集血清并分离胃组织。采用改良Guth法计算胃溃疡指数和溃疡抑制率；苏木精-伊红（HE）染色观察大鼠胃组织病理学变化；过碘酸希夫（PAS）染色观察胃组织黏膜糖蛋白表达；使用试剂盒测定胃组织中丙二醛（MDA）、超氧化物歧化酶（SOD）水平；TUNEL染色法比较各组大鼠胃组织细胞凋亡情况；免疫组化测定胃组织中Akt/NF-κB信号通路蛋白表达水平；Western blotting分析胃组织中炎症因子及Akt/NF-κB信号通路蛋白表达情况。结果 与模型组相比，胃康胶囊中、高剂量组的胃黏膜损伤较轻，出血性损伤明显减少，仅有少量血点，胃溃疡指数显著降低、溃疡抑制率显著升高（P＜0.01）；病理学变化明显减轻；高剂量组大鼠胃组织黏膜层PAS染色阳性表达百分比显著升高（P＜0.01）；中、高剂量组SOD活性显著升高（P＜0.05、0.01），MDA水平显著降低（P＜0.05、0.01）；各剂量组胃组织细胞凋亡率均显著降低（P＜0.01）；各剂量组胃组织p-Akt、p-NF-κB p65荧光显著减弱（P＜0.01）；中、高剂量组IL-6、TNF-α、p-Akt/Akt和p-NF-κB p65/NF-κB p65蛋白表达显著降低（P＜0.05、0.01）。结论 胃康胶囊治疗乙醇诱导胃溃疡模型大鼠效果显著，可有效减少溃疡面积，增加溃疡抑制率，保护溃疡组织，其作用机制可能与抑制Akt/NF-κB信号通路介导的炎症介质表达及降低氧化应激水平有关。

Objective To investigate the protective effect of gastric capsule against ethanol-induced gastric ulcer (GU) in rats based on the protein kinase B (Akt)/nuclear transcription factor-κB (NF-κB) signaling pathway, and to explore the possible mechanisms of its action.Methods SD rats were randomly divided into the control group, the model group, the omeprazole (positive drug, 20 mg·kg^-1) group, and the low-, medium-, and high-dose (480, 960, and 1 440 mg·kg^-1) groups of Weikang Capsules, with six rats in each group. Except for the control group, all other groups were given a single ig administration of 75% ethanol (10 mL·kg^-1) to establish the model. One hour after modeling, the corresponding drugs were ig administered to the drug groups, while the control group and the model group were given the same volume of 0.5% CMC-Na solution intragastrically once a day for three consecutive days. Six hours after the last intragastric administration on the third day, the rats were anesthetized, and blood was collected from the abdominal aorta. The serum was collected and the gastric tissues were isolated. The gastric ulcer index and ulcer inhibition rate were calculated using the modified Guth method; the histopathological changes of the gastric tissues were observed by hematoxylin-eosin (HE) staining; the expression of mucosal glycoprotein in the gastric tissues was observed by periodic acid-Schiff (PAS) staining; the levels of malondialdehyde (MDA) and superoxide dismutase (SOD) in the gastric tissues were determined using kits; the apoptosis of gastric tissue cells was compared by TUNEL staining; the expression levels of Akt/NF-κB signaling pathway proteins in the gastric tissues were determined by immunohistochemistry; and the expression of inflammatory factors and Akt/NF-κB signaling pathway proteins in the gastric tissues was analyzed by Western blotting.Results Compared with the model group, the gastric mucosal damage in the medium-and high-dose Weikang Capsules groups was milder, with significantly reduced hemorrhagic damage and only a few blood spots. The gastric ulcer index was significantly decreased and the ulcer inhibition rate was significantly increased (P<0.01). The pathological changes were significantly alleviated. The percentage of PAS staining positive expression in the gastric mucosal layer of the high-dose group was significantly increased (P<0.01). The SOD activity in the medium-and high-dose groups was significantly increased (P<0.05, 0.01), and the MDA level was significantly decreased (P<0.05, 0.01). The apoptosis rate of gastric tissue cells in all dose groups was significantly decreased (P<0.01). The fluorescence of p-Akt and p-NF-κB p65 in the gastric tissues of each dose group was significantly weakened (P<0.01). The protein expressions of IL-6, TNF-α, p-Akt/Akt, and p-NF-κB p65/NF-κB p65 in the medium-and high-dose groups were significantly decreased (P<0.05, 0.01).Conclusion The effect of Weikang Capsule in treating ethanol-induced gastric ulcer model rats was remarkable, which could effectively reduce the ulcer area, increase the ulcer inhibition rate and protect the ulcer tissue. The mechanism of action may be related to the inhibition of Akt/NF-κB signaling pathway-mediated expression of inflammatory mediators and the reduction of oxidative stress.

R285.5

贵州省科技厅基础研究计划项目（黔科合基础-ZK［2022］一般524）；贵州省中药炮制技术传承基地建设项目（黔中医药函（2024）22号）；2024年全国老药工传承工作室建设项目[黔中医药函（2024）42号]；贵州中医药大学国家与省级科技创新人才团队培育项目（贵中医TD合字［2023］005号）