木犀草素调控AMPK/ULK1通路对慢性萎缩性胃炎大鼠胃黏膜损伤的影响

doi:10.3969/j.issn.1006-6233.2026.01.04

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摘要 目的: 探索木犀草素调控腺苷酸活化蛋白激酶(AMPK)/Unc51样激酶1(ULK1)通路对慢性萎缩性胃炎大鼠胃黏膜损伤的影响。方法: 建立慢性萎缩性胃炎大鼠模型,并将其分为模型组、木犀草素组(80mg/kg)、抑制剂组(20mg/kg AMPK抑制剂Compound C)、木犀草素+激活剂组(80mg/kg木犀草素和200mg/kg AMPK激活剂AICAR),对照组为未建模大鼠,每组12只,持续灌胃给药12周。利用分光光度计测定胃黏膜血流量;ELISA法测定血清胃泌素(GAS)水平、血浆胃动素(MTL)及胃黏膜组织中IL-1β、TNF-α、SOD、MDA水平;HE染色观察胃黏膜组织病理学形态;TUNEL染色法测定胃黏膜组织细胞凋亡情况;透射电镜观察胃黏膜超微结构;免疫组化法测定胃黏膜组织B淋巴细胞瘤-2(Bcl-2)蛋白表达;Western blot法测定胃黏膜组织中AMPK/ULK1通路相关蛋白表达。结果: 与对照组比,模型组大鼠胃黏膜组织上皮细胞脱落,且炎性细胞浸润较多,胃黏膜壁细胞形状不规则,主细胞结构损害严重,胃黏膜血流量减少,GAS、MTL、SOD水平及Bcl-2蛋白表达量降低,病理学炎性评分、细胞凋亡率、IL-1β、TNF-α、MDA水平及p-AMPK、p-ULK1蛋白表达量升高(P<0.05);与模型组比,木犀草素组、抑制剂组胃黏膜组织病理损伤改善明显,胃黏膜血流量、GAS、MTL、SOD水平及Bcl-2蛋白表达均增加,病理学炎性评分、细胞凋亡率、IL-1β、TNF-α、MDA水平及p-AMPK、p-ULK1蛋白表达量降低(P<0.05);与木犀草素组比较,木犀草素+激活剂组大鼠上述指标的改善作用可被AMPK激活剂削弱(P<0.05)。结论: 木犀草素可能通过抑制AMPK/ULK1通路减轻慢性萎缩性胃炎大鼠胃黏膜损伤。

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关键词 ：木犀草素, 腺苷酸活化蛋白激酶, Unc51样激酶1, 慢性萎缩性胃炎

Abstract：Objective: To explore the effect of luteolin on gastric mucosal damage in rats with chronic atrophic gastritis by modulating the AMP-activated protein kinase (AMPK)/Unc51-like kinase 1 (ULK1) pathway. Methods: A chronic atrophic gastritis rat model was established and separated into a model group, a luteolin group (80mg/kg), an inhibitor group (20mg/kg AMPK inhibitor Compound C), and a luteolin+activator group (80mg/kg luteolin and 200mg/kg AMPK activator AICAR). The control group consisted of unmodeled rats. Each group consisted of 12 samples, receiving continuous gavage administration for 12 weeks. The spectrophotometer was used to measure gastric mucosal blood flow. ELISA method was used to measure serum gastrin (GAS), plasma motilin (MTL), and levels of IL-1β, TNF-α, SOD, and MDA in gastric mucosal tissue. HE staining was used to observe the pathological morphology of gastric mucosal tissue. TUNEL staining method was used to determine the apoptosis of gastric mucosal tissue cells. Transmission electron microscopy was used to observe the ultrastructure of gastric mucosa. Immunohistochemistry was used to measure the Bcl-2 protein in gastric mucosal tissue. In addition, Western blot was used to measure the AMPK/ULK1 pathway related proteins in gastric mucosal tissue. Results: Compared with the control group, the epithelial cells of the gastric mucosal tissue in the model group shed, and there was more infiltration of inflammatory cells. The shape of the gastric mucosal wall cells was irregular, and the main cell structure was severely injured. The gastric mucosal blood flow was reduced, and the levels of GAS, MTL, SOD, and the expression of Bcl-2 protein declined. While the pathological inflammatory score, apoptosis rate, levels of IL-1β, TNF-α, MDA, and expression of p-AMPK and p-ULK1 proteins increased (P<0.05). Compared with the model group, the gastric mucosal tissue pathological damage was prominently improved in the luteolin group and inhibitor group. The gastric mucosal blood flow, the levels of GAS, MTL, SOD, and the expression of Bcl-2 protein increased. While the pathological inflammatory score, apoptosis rate, levels of IL-1β, TNF-α, MDA, and expression of p-AMPK and p-ULK1 proteins declined (P<0.05). Compared with the luteolin group, the improvement effect of magnolol+activator group on the above indicators in rats can be weakened by AMPK activator (P<0.05). Conclusion: Luteolin may alleviate gastric mucosal injury in rats with chronic atrophic gastritis by inhibiting AMPK/ULK1 pathway.

Key words： Luteolin AMP-activated protein kinase Unc51-like kinase 1 Chronic atrophic gastritis

基金资助:2025-2026年度湖北省中医药管理局中医药科研项目,(编号:ZY2025Q017)

通讯作者: 孙俊

引用本文:

岳华强, 薛娟, 计春燕, 苏志威, 李诗旖, 丁毓雪, 程豪, 孙俊. 木犀草素调控AMPK/ULK1通路对慢性萎缩性胃炎大鼠胃黏膜损伤的影响[J]. 河北医学, 2026, 32(1): 20-27.
YUE Huaqiang, et al. The Effect of Luteolin on Gastric Mucosal Injury in Rats with Chronic Atrophic Gastritis via Regulation of the AMPK/ULK1 Pathway. HeBei Med, 2026, 32(1): 20-27.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2026.01.04 或 http://www.hbyxzzs.cn/CN/Y2026/V32/I1/20

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