目的 基于蛋白激酶B（Akt）/核因子-κB（NF-κB）信號(hào)通路研究胃康膠囊對(duì)乙醇誘導(dǎo)的大鼠胃潰瘍的保護(hù)作用，并探索其可能的作用機(jī)制。方法 SD大鼠隨機(jī)分為對(duì)照組、模型組、奧美拉唑（陽(yáng)性藥，20 mg·kg^-1）組和胃康膠囊低、中、高劑量（480、960、1 440 mg·kg^-1）組，每組6只。除對(duì)照組外，各組大鼠單次ig 75%乙醇（10 mL·kg^-1）造模。造模1 h后各給藥組ig相應(yīng)藥物，對(duì)照組、模型組ig等量0.5% CMC-Na溶液，每天1次，連續(xù)3 d，于第3天ig 6 h后，將大鼠麻醉，腹主動(dòng)脈采血，收集血清并分離胃組織。采用改良Guth法計(jì)算胃潰瘍指數(shù)和潰瘍抑制率；蘇木精-伊紅（HE）染色觀察大鼠胃組織病理學(xué)變化；過(guò)碘酸希夫（PAS）染色觀察胃組織黏膜糖蛋白表達(dá)；使用試劑盒測(cè)定胃組織中丙二醛（MDA）、超氧化物歧化酶（SOD）水平；TUNEL染色法比較各組大鼠胃組織細(xì)胞凋亡情況；免疫組化測(cè)定胃組織中Akt/NF-κB信號(hào)通路蛋白表達(dá)水平；Western blotting分析胃組織中炎癥因子及Akt/NF-κB信號(hào)通路蛋白表達(dá)情況。結(jié)果 與模型組相比，胃康膠囊中、高劑量組的胃黏膜損傷較輕，出血性損傷明顯減少，僅有少量血點(diǎn)，胃潰瘍指數(shù)顯著降低、潰瘍抑制率顯著升高（P＜0.01）；病理學(xué)變化明顯減輕；高劑量組大鼠胃組織黏膜層PAS染色陽(yáng)性表達(dá)百分比顯著升高（P＜0.01）；中、高劑量組SOD活性顯著升高（P＜0.05、0.01），MDA水平顯著降低（P＜0.05、0.01）；各劑量組胃組織細(xì)胞凋亡率均顯著降低（P＜0.01）；各劑量組胃組織p-Akt、p-NF-κB p65熒光顯著減弱（P＜0.01）；中、高劑量組IL-6、TNF-α、p-Akt/Akt和p-NF-κB p65/NF-κB p65蛋白表達(dá)顯著降低（P＜0.05、0.01）。結(jié)論 胃康膠囊治療乙醇誘導(dǎo)胃潰瘍模型大鼠效果顯著，可有效減少潰瘍面積，增加潰瘍抑制率，保護(hù)潰瘍組織，其作用機(jī)制可能與抑制Akt/NF-κB信號(hào)通路介導(dǎo)的炎癥介質(zhì)表達(dá)及降低氧化應(yīng)激水平有關(guān)。

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

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