麦角硫因对大鼠氧化损伤的保护作用研究

doi:10.19803/j.1672-8629.20250729

摘要/Abstract

摘要： 目的评估麦角硫因（EGT）对D-半乳糖（D-gal）诱导大鼠氧化损伤的保护作用,并探讨其潜在作用机制。方法通过腹腔注射D-gal溶液建立氧化应激损伤大鼠模型,并随机分为5组：空白组,模型组,EGT低、中、高剂量组（1.5、3.0、6.0 mg·kg^-1）。通过苏木精-伊红（HE）染色检测组织病理学变化;采用比色法检测组织中蛋白质氧化产物标志物蛋白质羰基、抗氧化酶和抗氧化物质标志物超氧化物歧化酶（SOD）和还原型谷胱甘肽（GSH）水平;利用蛋白质免疫印迹法（WB）验证EGT对大鼠肝脏中核因子E2相关因子2（Nrf2）和血红素加氧酶-1（HO-1）蛋白表达水平的影响。结果与模型组相比,中剂量组大鼠肝脏、肾脏和脾脏组织中GSH水平显著升高（P<0.05）,高剂量组大鼠肝脏、肾脏和脾脏组织中SOD活性明显增强（P<0.01）,中、高剂量组大鼠肾脏蛋白质羰基水平显著降低（P<0.01）,中、高剂量组大鼠脾脏蛋白质羰基水平显著降低（P<0.05）;组织病理学研究表明,经EGT干预后,大鼠肝脏、肾脏与脾脏组织的氧化损伤情况有显著改善;给药后大鼠肝脏Nrf2和HO-1蛋白表达水平显著上调（P<0.05）。结论 EGT能够改善D-gal诱导的大鼠氧化损伤,其潜在作用机制可能主要与Nrf2/HO-1信号通路有关。

关键词: 麦角硫因, D-半乳糖, 氧化应激, 抗氧化, Nrf2/HO-1信号通路, 大鼠, 作用机制

Abstract: Objective To investigate the protective effect of ergothioneine (EGT) against D-galactose(D-gal)-induced oxidative damage in rats and explore the underlying mechanisms. Methods An oxidative damage model was established by intraperitoneal injection of D-gal solution in rats which were randomly assigned to five experimental groups: the control group, model group, and groups treated with low-, medium- or high-dose of EGT (1.5, 3.0 and 6.0 mg·kg^-1). Histopathological changes were detected with hematoxylin-eosin (HE) staining. The levels of protein carbonyl, superoxide dismutase (SOD), and glutathione (GSH) were measured using colorimetric assays. Western blot analysis (WB) was used to determine the protein expression levels of nuclear factor erythroid 2-related factor 2 (Nrf2) and heme oxygenase-1 (HO-1). Results Compared to the model group, GSH levels were significantly increased in the liver, kidney, and spleen of rats in the medium-dose group (P<0.05), while SOD activity was markedly enhanced in these tissues in the high-dose group (P<0.01). Protein carbonyl levels in both the kidney (P<0.01) and spleen (P<0.05) were significantly decreased in medium-and high-dose groups. Histopathological findings revealed that oxidative damage to the hepatic, renal, and splenic tissues of rats was significantly ameliorated following EGT intervention. Additionally, the expressions of Nrf2 and HO-1 proteins in the liver were significantly upregulated (P<0.05). Conclusion A significant protective effect against D-gal-induced oxidative damage is exerted by EGT in rats, and the potential mechanism may be associated with the activation of the Nrf2/HO-1 signaling pathway.

Key words: Ergothioneine, D-Galactose, Oxidative Stress, Antioxidation, Nrf2/HO-1 Signaling Pathway, Rat, Mechanism of Action

中图分类号:

R994.11

刘欢, 易紫容, 张楠, 胡孟琦, 刘秀虹, 马昱明, 郑海云, 刘洋. 麦角硫因对大鼠氧化损伤的保护作用研究[J]. 中国药物警戒, 2026, 23(1): 95-100.

LIU Huan, YI Zirong, ZHANG Nan, HU Mengqi, LIU Xiuhong, MA Yuming, ZHENG Haiyun, LIU Yang. Protective Effects of Ergothioneine against Oxidative Damage in Rats[J]. Chinese Journal of Pharmacovigilance, 2026, 23(1): 95-100.

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https://zgywjj.magtechjournal.com/CN/Y2026/V23/I1/95

参考文献

[1] MENG Y, P.I. DAMITHRI WHD, WANG D. Isolation of 8 Strains of Beauveria and the Activity of Their Polysaccharides Antioxidation and Protective Activity against H₂O₂-Induced Oxidative Damage[J]. International Journal of Biological Macromolecules, 2025, 320: 146112.
[2] ZHANG ML, SONG HH, FENG YQ, et al.A Near-Infrared Light Responsive Nanoheterojunction for Antibacterial and Anti-Inflammatory Applications through Programmed ROS Regulation[J]. Journal of Colloid and Interface Science, 2025, 700: 138489.
[3] GLORIA EV-R, SPENCER BG. Reactive Oxygen Species (ROS) Regulates Different Types of Cell Death by Acting as a Rheostat[J]. Oxidative Medicine and Cellular Longevity, 2021, 2021(1): 9912436.
[4] CAROLINA S, GIORGIO Z, ALBERTO MM, et al.Oxidative Stress: Role of Physical Exercise and Antioxidant Nutraceuticals in Adulthood and Aging[J]. Oncotarget, 2018, 9(24): 17181-17198.
[5] NICOLE Y, MAZHAR P, JOHN JEC.Redox Changes and Cellular Senescence in Alzheimer’s Disease[J]. Redox Biology, 2024, 70: 103048.
[6] KIT-LEONG C, CHEN Q, JUDE JA, et al.Trends in Polysaccharide-Based Hydrogels for Skin Anti-Aging and Skin Antioxidant[J]. International Journal of Biological Macromolecules, 2025, 319: 145366.
[7] LIANG HM, ZHANG LQ, WAN WR, et al.Ethanol Extract of Momordica cochinchinensis Alleviates Hydrogen Peroxide-Induced Oxidative Damage in SH-SY5Y Cells by Regulating Nrf2/Keap1 Signaling Pathway[J]. Chinese Traditional and Herbal Drugs(中草药), 2025, 56(16): 5826-5836.
[8] GAO CC.CK2-Mediated Phosphorylation and Nitrosylation of 6PGD under Oxidative Stress Maintain the Survival of Hepatocellular Carcinoma Cells[D]. Nanchang: Nanchang University, 2025.
[9] SOYEON J, PETER MK.A Systematic Review on Advances in Management of Oxidative Stress-Associated Cardiovascular Diseases[J]. Antioxidants, 2024, 13(8): 923.
[10] GUAN BT, LI W, ZHAO F, et al.Protective Effects of Giant Salamander Bioactive Peptides on D-Galactose Induced Oxidative Damage in Mice[J]. Science and Technology of Food Industry(食品工业科技), 2021, 42(16): 344-352.
[11] LI N.Mechanisms of Ergothioneine in Alleviating Cognitive Dysfunction in Alzheimer's Disease[D]. Changsha: Central South University of Forestry and Technology, 2025.
[12] LIU XQ, QIU XF, LIU Z.Research Progress on the Functions, Preparation and Application of Ergothioneine[J]. China Food & Drug Administration Magazine(中国食品药品监管), 2024(6): 116-128.
[13] RONY AS, AMER A, ASRIADI, et al. Ergothioneine as a Functional Nutraceutical: Mechanisms, Bioavailability, and Therapeutic Implications[J]. The Journal of Nutritional Biochemistry, 2025, 145: 110006.
[14] WEN TT, CHEN WJ, WANG FJ, et al.The Roles and Functions of Ergothioneine in Metabolic Diseases[J]. The Journal of Nutritional Biochemistry, 2025, 141: 109895.
[15] DU Y.Rhubarb Decoction Regulates the Mechanism of Liver Oxidative Stress Injury in MHE Rats through STAT Signaling Pathway[D]. Nanning: Guangxi University of Chinese Medicine, 2025.
[16] STEVEN JF, DANIEL SK, MARINA SH, et al.Reactive Oxygen Species in Metabolic and Inflammatory Signaling[J]. Circulation Research, 2018, 122(6): 877-902.
[17] GU W.Evaluation of Protein Oxidative Damage and Functional Impairment Based on Protein Carbonylation and Significance of Its Application[D]. Dalian: Dalian Medical University, 2022.
[18] AMR AMAE-S, ABDULSALAM NM, JITENDRA G, et al.Combating Oxidative Stress in Non-Alcoholic Fatty Liver Disease: from Mechanisms to Therapeutic Strategies[J]. Pathology-Research and Practice, 2025, 272: 156053.
[19] LI SX, YUAN GX, MA Y, et al.Study on Immunomodulatory Effect of Guipi Pills on D-Galactose-Induced Aging Mice[J]. China Pharmacy(中国药房), 2023, 34(12): 1426-1430.
[20] CHEN YL, LI Y, CHEN ZQ, et al.Protective Effect of 6-Shogaol on D-Galactose-Induced Aging of C57BL/6 Mice[J]. Modern Food Science and Technology(现代食品科技), 2024, 40(11): 30-37.
[21] AGNIESZKA L, MILENA D, ELZBIETA P, et al.Role of Nrf2/HO-1 System in Development, Oxidative Stress Response and Diseases: an Evolutionarily Conserved Mechanism[J]. Cellular and Molecular Life Sciences, 2016, 73(17): 3221-3247.
[22] ALESSIO A, SALIL S, RICHARD CMS, et al.Targeting the Nrf2-Keap1 Antioxidant Defence Pathway for Neurovascular Protection in Stroke[J]. The Journal of Physiology, 2011, 589(17): 4125-4136.
[23] YUAN XW, LI L, ZHANG Y, et al.Heme Oxygenase 1 Alleviates Nonalcoholic Steatohepatitis by Suppressing Hepatic Ferroptosis[J]. Lipids in Health and Disease, 2023, 22(1): 99.
[24] CHEN L, ZHANG LP, YE XJ, et al.Ergothioneine and Its Congeners: Anti-Ageing Mechanisms and Pharmacophore Biosynthesis[J]. Protein & Cell, 2024, 15(3): 191-206.
[25] CHEN FY, WANG BT, SUN X, et al.Ergothioneine Improves Cognitive Function by Ameliorating Mitochondrial Damage and Decreasing Neuroinflammation in a D-Galactose-Induced Aging Model[J]. Food & Function, 2024, 15(23): 11686-11696.
[26] CHEAH IK, RICHARD MYT, TERRY SZY, et al.Administration of Pure Ergothioneine to Healthy Human Subjects: Uptake, Metabolism, and Effects on Biomarkers of Oxidative Damage and Inflammation[J]. Antioxidants & Redox Signaling, 2017, 26(5): 193-206.