牛蒡子苷元对四氧嘧啶诱导糖尿病小鼠肝损伤的保护作用

目的：探究牛蒡子苷元（arctigenin，ATG）对于糖尿病小鼠肝损伤的保护作用。方法：通过四氧嘧啶诱导雄性ICR小鼠建立糖尿病模型，设置对照组、模型组、阳性二甲双胍（metformin，Met）组以及ATG高、中、低剂量组（120、90、60 mg/kg mb），测定小鼠血清中谷丙转氨酶（alanine aminotransferase，ALT）和谷草转氨酶（asparate aminotransferase，AST）活力以及炎症因子白细胞介素-6（interleukin-6，IL-6）和肿瘤坏死因子-α（tumor necrosis factor-α，TNF-α）质量浓度；分析肝脏内谷胱甘肽（glutathione，GSH）、过氧化氢酶（catalase，CAT）和超氧化物歧化酶（superoxide dismutase，SOD）水平；对比肝脏染色切片组织形态、组织Toll样受体4（toll-like receptors 4，TLR4）、髓样分化因子88（myeloid differentiation factor 88，MyD88）、核因子κB p65（nuclear factor κB p65，NF-κB p65）信号通路中相关蛋白表达情况。结果：与模型组相比，ATG高剂量干预极显著降低了糖尿病小鼠血清中ALT活力和AST活力（P＜0.01）；ATG高、中剂量极显著降低了炎症因子IL-6、TNF-α质量浓度（P＜0.01）；ATG高剂量极显著提高了糖尿病小鼠肝脏内CAT、SOD活力（P＜0.01），显著提高GSH含量（P＜0.05）；ATG高、中剂量明显改善了肝脏组织细胞形态，使苏木精-伊红染色切片中细胞内染红面积增大，细胞空泡和出血区域减少；ATG高剂量显著降低了肝脏内TLR4、MyD88和NF-κB p65蛋白表达量（P＜0.05、P＜0.01）。ATG保护糖尿病肝损伤作用机理可能是通过降低TLR4、MyD88、NF-κB p65炎性通路中关键蛋白的表达水平，抑制下游的TNF-α、IL-6等炎症因子表达，进而降低氧化应激水平，改善肝脏组织损伤程度。结论：ATG对糖尿病性肝损伤具有保护作用，本研究可为ATG用于糖尿病性肝损伤的防治提供参考依据。

Protective Effect of Arctigenin on Liver Injury in Diabetic Mice Induced by Alloxan

Objective: To explore the protective effect of arctigenin (ATG) on liver injury in diabetic mice. Methods: Alloxan was used to induce diabetes in male ICR mice. Six groups of mice were set up: control, model, positive control (metformin, Met), and high-, medium-, and low-dose ATG (120, 90 and 60 mg/kg mb). The activities of alanine aminotransferase (ALT) and asparate aminotransferase (AST) and the concentrations of the inflammatory cytokine interleukin-6 (IL-6) and tumor necrosis factor-α (TNF-α) were in the serum determined. Liver glutathione (GSH), catalase (CAT) and superoxide dismutase (SOD) levels were analyzed, and histomorphological observation of the liver was performed after hematoxylin and eosin staining. Protein expression levels involved in the toll-like receptors (TLR4), myeloid differentiation factor 88 (MyD88) and nuclear factor κB p65 (NF-κB p65) signaling pathways were measured. Results: Compared with the model group, high-dose ATG significantly reduced ALT and AST activities in the serum of diabetic mice (P < 0.01); high- and medium-dose ATG significantly reduced serum IL-6 and TNF-α levels (P < 0.01); high-dose ATG significantly increased liver CAT and SOD activities (P < 0.01) as well as GSH levels (P < 0.05); high- and medium-dose ATG significantly improved the cellular morphology of liver tissue, increasing the red-stained area of cells in liver slices and reducing cell vacuoles and bleeding areas. High-dose ATG significantly reduced the protein expression of TLR4, MyD88 and NF-κB p65 in the liver (P < 0.01 and P < 0.05). The hepatoprotective mechanism of ATG may be related to reducing the expression of key proteins in the TLR4, MyD88 and NF-κB p65 signaling pathways, and inhibiting the expression of downstream inflammatory factors, such as NF-κB, TNF-α and IL-6, thereby reducing the level of oxidative stress. Conclusion: ATG has a protective effect on diabetic liver injury. This study provides a reference for the application of ATG in the prevention and treatment of diabetic liver injury.