脯氨酸加格列净通过抑制DPP4/NOX1介导的氧化应激反应改善代谢相关脂肪性肝病小鼠肝脂肪变性*

doi:10.3969/j.issn.1672-5069.2026.04.003

摘要/Abstract

摘要： 目的研究脯氨酸加格列净(JAGN)改善代谢相关脂肪性肝病(MAFLD)的作用机制。方法将30只C57BL/6小鼠随机分为对照组、模型组和干预组,每组10只,采用高脂饮食喂养建立MAFLD模型,观察JAGN干预的作用。取肝组织匀浆检测丙二醛(MDA)、谷胱甘肽(GSH)和超氧化物歧化酶(SOD)水平,采用免疫荧光法检测活性氧(ROS)水平,采用TUNEL染色法检测细胞凋亡,分别采用实时荧光定量PCR法和蛋白质免疫印记法检测肽基肽酶-4(DPP4)和NADPH氧化酶1(NOX1)mRNA和蛋白表达水平。结果模型组小鼠肝组织可见肝小叶形态紊乱和肝细胞脂肪变性,而JAGN干预组肝组织脂肪变性减轻;模型组肝组织MDA水平为(4.5±0.6)μmol/L,显著高于对照组[(2.7±0.4)μmol/L,P<0.05],而干预组为(3.1±0.9)μmol/L,显著低于模拟组(P<0.05),模型组肝组织GSH和SOD水平分别为(6.5±1.1)mg/g和(0.1±0.1)U/mg,均显著低于对照组[分别为(8.5±1.4)mg/g和(0.5±0.1)U/mg,P<0.05],而干预组分别为(9.7±2.1)mg/g和(0.3±0.1)U/mg,均显著高于模型组(P<0.05);模型组肝组织ROS水平显著高于对照组(P<0.05),而干预组肝组织ROS水平显著低于模型组(P<0.05),模型组肝组织细胞凋亡显著,而干预组肝组织细胞凋亡显著减少;模型组肝组织DPP4活性显著高于对照组(P<0.05),而干预组肝组织DPP4活性显著低于模型组(P<0.05);MAFLD模型组小鼠肝组织DPP4和NOX1基因和蛋白表达显著高于对照组(P<0.05),而干预组肝组织DPP4和NOX1基因和蛋白表达显著低于模型组(P<0.05)。结论 JAGN能够通过抑制DPP4/NOX1介导的氧化应激反应改善MAFLD小鼠肝脂肪变性。

Abstract: Objective This experiment aimed to explore the potential mechanism by which Janagliflozin (JAGN) ameliorates liver steatosis in mice with high-fat diet-induced metabolic dysfunction-associated fatty liver disease (MAFLD) by inhibiting dipeptidyl peptidase-4(DPP4)/NOX1 mediated oxidative stress. Method 30 C57BL/6 mice were randomly divided into control, model and intervention group, with 10 mice in each. The model was established by high fat diet feeding, and intervention was completed by JAGN gavage. Hepatic homogenate malondialdehyde (MDA), glutathione (GSH) and superoxide dismutase (SOD) level was routinely detected. ROS level was determined by immunofluorescence, cell apoptosis was finished by TUNEL staining, DPP4 and nicotinamide adenine dinucleotide phosphate oxidase 1 (NOX1) mRNA an their protein expression were assayed by real time fluorescence quantitative PCR and Western blot. Results Liver steatosis was found in model mice, suggesting the model was successfully established, and in JAGN-intervened group, liver steatosis was obviously ameliorated; hepatic homogenate MDA level was (4.5±0.6)μmol/L, much higher than [(2.7±0.4)μmol/L, P<0.05] in the control, while it turned to (3.1±0.9)μmol/L in the intervention group, much lower than in the model (P<0.05), GSH and SOD levels in the model were (6.5±1.1)mg/g and (0.1±0.1)U/mg, both much lower than [(8.5±1.4)mg/g and (0.5±0.1)U/mg, respectively, P<0.05] in the control, while they turned to (9.7±2.1)mg/g and (0.3±0.1)U/mg in the JAGN-intervened group, much higher than in the model (P<0.05); hepatic ROS level in the model was much higher than in the control (P<0.05), while it decreased greatly in the intervention group (P<0.05); apoptosis was obvious in the model, and it alleviated in the intervention group; hepatic DPP4 activity in the model was higher than in the control (P<0.05), while it decreased greatly in the intervention group(P<0.05); hepatic DPP4 and NOX1 mRNA level and protein expression in the model were higher or stronger than in the control(P<0.05), while they became lower or weaker in the JAGN-intervened group (P<0.05). Conclusion Janagliflozin could alleviate liver steatosis in mice with MAFLD, which might be related to the inhibition of DPP4/NOX1 mediated oxidative stress.

Key words: Metabolic dysfunction-associated fatty liver disease, Liver steatosis, Sodium glucose cotransporter 2 inhibitor, Oxidative stress, Mice

刘江, 袁涵, 凌芬, 李东海. 脯氨酸加格列净通过抑制DPP4/NOX1介导的氧化应激反应改善代谢相关脂肪性肝病小鼠肝脂肪变性^*[J]. 实用肝脏病杂志, 2026, 29(4): 489-492.

Liu Jiang, Yuan Han, Ling Fen, et al. Janagliflozin ameliorates liver steatosis in mice with high-fat diet-induced metabolic dysfunction-associated fatty liver disease by inhibiting DPP4/NOX1 mediated oxidative stress[J]. Journal of Practical Hepatology, 2026, 29(4): 489-492.

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脯氨酸加格列净通过抑制DPP4/NOX1介导的氧化应激反应改善代谢相关脂肪性肝病小鼠肝脂肪变性^*

Janagliflozin ameliorates liver steatosis in mice with high-fat diet-induced metabolic dysfunction-associated fatty liver disease by inhibiting DPP4/NOX1 mediated oxidative stress

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