该研究的目的是探究小麦肽对乙醇造成的胃黏膜损伤的保护作用及其机制。使用小麦肽进行处理后,乙醇诱导小鼠胃黏膜损伤模型和人胃黏膜上皮细胞(human gastric mucosal epithelial cell, GES-1)细胞损伤模型,观察小鼠体重变化和胃组织损伤状况,评估氧化应激、炎症和自噬相关蛋白表达水平。小麦肽预处理显著改善了乙醇诱导的小鼠体重降低,提高了胃组织和GES-1细胞内抗氧化酶活力和一氧化氮(NO)含量,减少脂质过氧化发生。病理组织切片显示,小麦肽预处理后,胃组织损伤显著减少。此外,小麦肽降低了组织内促炎因子表达,并通过抑制GES-1细胞中PI3K/AKT/mTOR通路激活,提高了LC3-Ⅱ蛋白表达。小麦肽可以通过调节抗氧化能力和促炎因子表达,抑制PI3K/mTOR通路激活等方式,改善乙醇诱导的胃黏膜损伤。
The objective of the study was to investigate the protective effect of wheat peptides on gastric mucosal injury caused by ethanol and its mechanism.After treatment with wheat peptides, ethanol induced gastric mucosal injury model in mice and human gastric mucosal epithelial cell (GES-1) injury model was used to observe the changes in body weight and gastric tissue damage and to assess the expression levels of oxidative stress, inflammation and autophagy-related proteins.Wheat peptides pretreatment significantly improved ethanol-induced weight loss in mice, increased antioxidant enzyme activity and nitric oxide (NO) content, and reduced lipid peroxidation in gastric tissues and GES-1 cells.Pathological tissue sections showed a significant reduction in gastric tissue damage after wheat peptides pretreatment.In addition, wheat peptides reduced tissue expression of pro-inflammatory factors and increased LC3-Ⅱ protein expression by inhibiting PI3K/AKT/mTOR pathway activation in GES-1 cells.Wheat peptides could improve ethanol-induced gastric mucosal injury by modulating antioxidant capacity, inhibiting pro-inflammatory factor expression and PI3K/mTOR pathway activation.
[1] AIHARA T, NAKAMURA E, AMAGASE K, et al.Pharmacological control of gastric acid secretion for the treatment of acid-related peptic disease:Past, present, and future[J].Pharmacology & Therapeutics, 2003, 98(1):109-127.
[2] BEHRMAN S W.Management of complicated peptic ulcer disease[J].Archives of Surgery, 2005, 140(2):201-208.
[3] RIEZZO G, CHILOIRO M, MONTANARO S.Protective effect of amtolmetin guacyl versus placebo diclofenac and misoprostol in healthy volunteers evaluated as gastric electrical activity in alcohol-induced stomach damage[J].Digestive Diseases and Sciences, 2001, 46(8):1797-1804.
[4] DE ARAÚJO E R D, GUERRA G C B, ARAÚJO D F S, et al.Gastroprotective and antioxidant activity of Kalanchoe brasiliensis and Kalanchoe pinnata leaf juices against indomethacin and ethanol-induced gastric lesions in rats[J].International Journal of Molecular Sciences, 2018, 19(5):1265.
[5] PAN J S, HE S Z, XU H Z, et al.Oxidative stress disturbs energy metabolism of mitochondria in ethanol-induced gastric mucosa injury[J].World Journal of Gastroenterology, 2008, 14(38):5857-5867.
[6] ZHOU D, YANG Q, TIAN T, et al.Gastroprotective effect of gallic acid against ethanol-induced gastric ulcer in rats:Involvement of the Nrf2/HO-1 signaling and anti-apoptosis role[J].Biomedicine & Pharmacotherapy=Biomedecine & Pharmacotherapie, 2020, 126:110075.
[7] CHANG W L, BAI J, TIAN S B, et al.Autophagy protects gastric mucosal epithelial cells from ethanol-induced oxidative damage via mTOR signaling pathway[J].Experimental Biology and Medicine, 2017, 242(10):1025-1033.
[8] KAN J T, HOOD M, BURNS C, et al.A novel combination of wheat peptides and fucoidan attenuates ethanol-induced gastric mucosal damage through anti-oxidant, anti-inflammatory, and pro-survival mechanisms[J].Nutrients, 2017, 9(9):978.
[9] HERNÁNDEZ-MUÑOZ R, DÍAZ-MUÑOZ M, LÓPEZ V, et al.Balance between oxidative damage and proliferative potential in an experimental rat model of CCI[J].Hepatology, 1997, 26(5):1100-1110.
[10] HERNÁNDEZ-MUÑOZ R, MONTIEL-RUÍZ C, VÁZQUEZ-MARTÍNEZ O.Gastric mucosal cell proliferation in ethanol-induced chronic mucosal injury is related to oxidative stress and lipid peroxidation in rats[J].Laboratory Investigation, 2000, 80(8):1161-1169.
[11] YANG Y, YIN B, LV L, et al.Gastroprotective effect of aucubin against ethanol-induced gastric mucosal injury in mice[J].Life Sciences, 2017, 189:44-51.
[12] YIN H, PAN X C, SONG Z X, et al.Protective effect of wheat peptides against indomethacin-induced oxidative stress in IEC-6 cells[J].Nutrients, 2014, 6(2):564-574.
[13] VILLALOBOS-GARCÍA D, HERNÁNDEZ-MUÑOZ R.Catalase increases ethanol oxidation through the purine catabolism in rat liver[J].Biochemical Pharmacology, 2017, 137:107-112.
[14] RAO R, BAKER R D, BAKER S S.Inhibition of oxidant-induced barrier disruption and protein tyrosine phosphorylation in Caco-2 cell monolayers by epidermal growth factor[J].Biochemical Pharmacology, 1999, 57(6):685-695.
[15] BHATTACHARYYA A, CHATTOPADHYAY R, MITRA S, et al.Oxidative stress:An essential factor in the pathogenesis of gastrointestinal mucosal diseases[J].Physiological Reviews, 2014, 94(2):329-354.
[16] GUMA M, STEPNIAK D, SHAKED H, et al.Constitutive intestinal NF-κB does not trigger destructive inflammation unless accompanied by MAPK activation[J].Journal of Experimental Medicine, 2011, 208(9):1889-1900.
[17] AL ASMARI A, AL SHAHRANI H, AL MASRI N, et al.Vanillin abrogates ethanol induced gastric injury in rats via modulation of gastric secretion, oxidative stress and inflammation[J].Toxicology Reports, 2016, 3:105-113.
[18] YANG C Y, SONG Y L, WANG H.Suppression of RAGE and TLR9 by ketamine contributes to attenuation of lipopolysaccharide-induced acute lung injury[J].Journal of Investigative Surgery, 2017, 30(3):177-186.
[19] KOBAYASHI T, OHTA Y, YOSHINO J, et al.Teprenone promotes the healing of acetic acid-induced chronic gastric ulcers in rats by inhibiting neutrophil infiltration and lipid peroxidation in ulcerated gastric tissues[J].Pharmacological Research, 2001, 43(1):23-30.
[20] YU L L, LI R J, LIU W, et al.Protective effects of wheat peptides against ethanol-induced gastric mucosal lesions in rats:Vasodilation and anti-inflammation[J].Nutrients, 2020, 12(8):2355.
[21] PUGSLEY H R.Assessing autophagic flux by measuring LC3, p62, and LAMP1 co-localization using multispectral imaging flow cytometry[J].Journal of Visualized Experiments: JoCE, 2017(125):55637.
[22] RAMKUMAR A, MURTHY D, RAJA D A, et al.Classical autophagy proteins LC3B and ATG4B facilitate melanosome movement on cytoskeletal tracks[J].Autophagy, 2017, 13(8):1331-1347.
