谷氨酰胺、姜黄素组方对酒精性胃粘膜损伤的保护作用

陆海霞; 徐莹; 潘美辰; 唐天培; 赵建云; 葛磊

doi:10.13386/j.issn1002-0306.2023030217

谷氨酰胺、姜黄素组方对酒精性胃粘膜损伤的保护作用

Protective Effect of a Combined Glutamine and Curcumin Formulation on Alcoholic Gastric Mucosal Damage

摘要

摘要: 目的：旨在探讨谷氨酰胺、姜黄素组方对乙醇致大鼠胃粘膜损伤的保护作用及机制。方法：将50只SPF级健康SD雄性大鼠随机分为空白组、模型对照组、西米替丁组、高剂量组、低剂量组5组。连续30 d口服灌胃给药后，除空白组外，其余各组均在无水乙醇造模后处死。通过H&E染色观察胃粘膜组织病理学变化情况，采用试剂盒测定血清丙二醛（malondialdehyde，MDA）、一氧化氮（NO）含量和谷胱甘肽过氧化物酶（Glutathioneperoxidase，GSH-Px）活性，并测定组织中前列腺素E₂（PGE₂）含量水平和血红素加氧酶-1（heme oxygenase-1，HO-1）、NADPH醌氧化还原酶（NADPH Quinone Oxidoreductase 1，NQO1）、抗氧化相关基因核因子-E₂相关因子2（Nuclear factor-E₂ related factor₂，Nrf2）、丝氨酸蛋白激酶-3β（Glycogen synthase kinase-3β，GSK-3β）的表达情况。结果：西米替丁组、高剂量给药组的胃粘膜出血等损伤情况较模型组（P<0.05）均有所缓解，高剂量给药组的效果更明显。此外，模型组MDA含量和GSH-P_X活性明显增加，NO和PGE₂含量明显下降（P<0.05），抗氧化相关基因HO-1、NQO1和Nrf2表达受到明显抑制，GSK-3β表达明显增加。与模型组相比，西咪替丁组和高剂量给药组MDA含量和GSH-Px活性显著下降，NO、PGE₂含量显著上升（P<0.05），抗氧化相关基因HO-1、NQO1、Nrf2得到显著恢复（P<0.05），GSK-3β被抑制（P<0.05）。结论：组方对乙醇引起的急性胃黏膜损伤有抑制作用，其作用机制推测与Keap1-Nrf2-ARE氧化应激通路有关。

Abstract: Objective: This study aimed to investigate the protective effect and underlying mechanism of a combined glutamine and curcumin formulation on ethanol-induced gastric mucosal damage in rats. Method: A total of fifty SPF-grade healthy SD male rats were randomly partitioned into five groups: A normal group, a model control group, a cimetidine group, a high-dose treatment group, and a low-dose treatment group. After a period of 30 days marked by oral gavage administration, all groups, with the exception of the normal group, were euthanized post anhydrous ethanol-induced modeling. The histopathological alterations in the gastric mucosa were observed via hematoxylin & eosin (H&E) staining. Furthermore, serum levels of malondialdehyde (MDA), nitric oxide (NO), and glutathione peroxidase (GSH-PX) were ascertained using a specific reagent kit. Concurrently, the concentration of prostaglandin E₂ (PGE₂) within the tissue and the expression levels of heme oxygenase-1 (HO-1), NADPH quinone oxidoreductase (NQO1), the antioxidant-related nuclear factor-E2-related factor 2 (Nrf2) gene, and glycogen synthase kinase-3β (GSK-3β) were evaluated. Results: In the cimetidine and high-dose treatment groups, the incidence of gastric mucosal bleeding and other forms of injury were noticeably mitigated (P<0.05) compared to the model control group, with the high-dose treatment group demonstrating a more pronounced effect. Moreover, the model control group exhibited a significant elevation in MDA content and GSH-P_X activity and a concurrent decline in NO and PGE₂ levels (P<0.05). The expression of antioxidant-related genes, namely, HO-1, NQO1, and Nrf2, was significantly suppressed (P<0.05), whereas GSK-3β expression was markedly increased. In contrast, in comparison to the model control group, the cimetidine and high-dose treatment groups manifested a significant reduction in MDA content and GSH-PX activity, while NO and PGE₂ levels notably increased (P<0.05). The expression of the antioxidant-related genes HO-1, NQO1, and Nrf2 was significantly returned to normal (P<0.05), and GSK-3β expression was suppressed (P<0.05). Conclusion: The combined formulation appears to exert an inhibitory effect on ethanol-induced acute gastric mucosal damage. This effect is hypothesized to be associated with the Keap1-Nrf2-ARE oxidative stress signaling pathway.