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  

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

作　　者：由高飞 唐金鑫 孙航 刘士伟 李秋阳 徐萍 于雷[1] 毕云枫[1] YOU Gaofei;TANG Jinxin;SUN Hang;LIU Shiwei;LI Qiuyang;XU Ping;YU Lei;BI Yunfeng(College of Food Science and Engineering,Jilin Agricultural University,Changchun 130118,China)

机构地区：[1]吉林农业大学食品科学与工程学院,吉林长春130118

出　　处：《食品科学》2022年第19期184-190,共7页Food Science

基　　金：吉林省科技厅重点科技研发项目(20180201046NY)。

摘　　要：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 m_(b)),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 factorκB 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。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 m_(b)).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 factorκB 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-αlevels(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-αand 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.

关 键 词：牛蒡子苷元 糖尿病 肝损伤 保护作用 作用机理 

分 类 号：TS201.4[轻工技术与工程—食品科学]