三七白及粉通过Nrf2/Gpx4介导的铁死亡改善脑出血型应激性溃疡大鼠的胃黏膜损伤

doi:10.3969/j.issn.1006-6233.2023.08.07

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摘要 目的: 探究三七白及粉通过Nrf2/Gpx4介导的铁死亡对脑出血型应激性溃疡大鼠胃黏膜损伤的保护作用。方法: 按照随机数字表法将60只大鼠分为NC组、SGU组、三七白及粉低剂量组(三七白及粉L组)、三七白及粉中剂量组(三七白及粉M组)、三七白及粉高剂量组(三七白及粉H组)、三七白及粉高剂量+Nrf2特异性抑制剂ML385组(三七白及粉H+ML385组),每组10只。对大鼠进行神经功能评分;测定胃黏膜溃疡指数;HE染色检测胃组织病理学变化;检测胃组织中Fe²⁺、MDA含量及SOD活性;DHE荧光染色法检测胃组织中ROS水平;蛋白质印迹检测胃黏膜组织中Nrf2、Gpx4和SLC7A11蛋白表达。结果: 和NC组相比,SGU组大鼠神经功能评分、胃黏膜溃疡指数、Fe²⁺、MDA含量及ROS水平增加,SOD活性降低(P<0.05);和SGU组相比,三七白及粉L、M、H组大鼠神经功能评分、胃黏膜溃疡指数、Fe²⁺、MDA含量及ROS水平明显降低,SOD活性升高(P<0.05);和三七白及粉H组相比,三七白及粉H+ML385组大鼠神经功能评分、胃黏膜溃疡指数、Fe²⁺、MDA含量及ROS水平明显升高,SOD活性降低(P<0.05)。和NC组相比,SGU组大鼠胃黏膜组织中Nrf2、Gpx4和SLC7A11蛋白表达明显降低(P<0.05);和SGU组相比,三七白及粉L、M、H组大鼠胃黏膜组织中Nrf2、Gpx4和SLC7A11蛋白表达均明显增加,且呈剂量依赖(P<0.05);三七白及粉H+ML385组大鼠胃黏膜组织中Nrf2、Gpx4和SLC7A11蛋白表达明显低于三七白及粉H组(P<0.05)。结论: 三七白及粉对脑出血型应激性溃疡大鼠胃黏膜损伤发挥保护作用,其机制和激活Nrf2/Gpx4通路抑制铁死亡相关。

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关键词 ：三七白及粉, Nrf2/Gpx4, 铁死亡, 脑出血型应激性溃疡, 胃黏膜损伤

Abstract：Objective: To investigate the protective effect of Panax notoginseng powder on gastric mucosal injury in rats with cerebral hemorrhagic stress ulcers via Nrf2/Gpx4-mediated iron death. Methods: A total of 60 rats were divided into NC group, SGU group, Panax notoginseng powder low dose group (Panax notoginseng powder L group), Panax notoginseng powder medium dose group (Panax notoginseng powder M group), Panax notoginseng powder high dose group (Panax notoginseng powder H group), Panax notoginseng powder high dose + Nrf2 specific inhibitor ML385 group (Panax notoginseng powder H + ML385 group) according to the random number table method, 10 rats in each group. The rats were scored for neurological function; the ulcer index of gastric mucosa was measured; HE staining was performed to detect histopathological changes in gastric tissues; Fe²⁺, MDA content and SOD activity were detected in gastric tissues; ROS levels in gastric tissues were detected by DHE fluorescence staining; Nrf2, Gpx4 and SLC7A11 protein expression in gastric mucosa tissues were detected by protein blotting. Results: Compared with the NC group, the neurological function score, gastric mucosal ulcer index, Fe²⁺, MDA content and ROS level increased and SOD activity decreased in the SGU group (P<0.05); compared with the SGU group, the neurological function score, gastric mucosal ulcer index, Fe²⁺, MDA content and ROS level decreased significantly and SOD activity increased in the Panax ginseng powder L, M and H groups ( P<0.05); compared with the Panax ginseng powder H group, the neurological function score, gastric mucosal ulcer index, Fe²⁺, MDA content and ROS level of rats in the Panax ginseng powder H+ML385 group were significantly higher and SOD activity was lower (P<0.05). Compared with the NC group, Nrf2, Gpx4 and SLC7A11 protein expression in the gastric mucosa tissues of rats in the SGU group were significantly decreased (P<0.05); compared with the SGU group, Nrf2, Gpx4 and SLC7A11 protein expression in the gastric mucosa tissues of rats in the Panax ginseng powder L, M and H groups were significantly increased in a dose-dependent manner (P<0.05); panax ginseng white and powder H+ Nrf2, Gpx4 and SLC7A11 protein expression in gastric mucosal tissues of rats in ML385 group were significantly lower than those in Panax notoginseng powder H groups (P<0.05). Conclusion: Panax notoginseng powder exerts a protective effect on gastric mucosal injury in rats with cerebral hemorrhagic stress ulcers, and the mechanism is related to the activation of Nrf2/Gpx4 pathway to inhibit iron death.

Key words： Panax notoginseng powder Nrf2/Gpx4 ron death Cerebral hemorrhagic stress ulcer Gastric mucosal injury

基金资助:河北省中医药管理局项目,(编号:2019454)

引用本文:

安凯, 郭沛然, 孙玉凤. 三七白及粉通过Nrf2/Gpx4介导的铁死亡改善脑出血型应激性溃疡大鼠的胃黏膜损伤[J]. 河北医学, 2023, 29(8): 1267-1274.
AN Kai, et al. Panax Nnotoginseng Powder Ameliorates Gastric Mucosal Injury via Nrf2/Gpx4-Mediated Iron Death in Rats with Cerebral Hemorrhagic Stress Ulcers. HeBei Med, 2023, 29(8): 1267-1274.

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http://www.hbyxzzs.cn/CN/10.3969/j.issn.1006-6233.2023.08.07 或 http://www.hbyxzzs.cn/CN/Y2023/V29/I8/1267

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