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 30d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(Glu-tathioneperoxidase,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-PX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 glut-amine 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 mode-ling.The histopathological alterations in the gastric mucosa were observed via hematoxylin&eosin(H&E)staining.Furt-hermore,serum levels of malondialdehyde(MDA),nitric oxide(NO),and glutathione peroxidase(GSH-PX)were ascer-tained 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 cime-tidine 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 pron-ounced effect.Moreover,the model control group exhibited a significant elevation in MDA content and GSH-PX 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 sign-aling pathway.
维普
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