槲皮素通过Nrf2通路对糖尿病大鼠胰腺氧化损伤的拮抗作用机制  

Antagonistic Effect of Quercetin against Oxidative Pancreatic Injury in Diabetic Rats via Nrf2 Pathway

作　　者：李阳 苏艳瑜 李国豪 李琪[1] 王宇翔 丁玉松[1] LI Yang;SU Yanyu;LI Guohao;LI Qi;WANG Yuxiang;DING Yusong(School of Medicine,Shihezi University,Shihezi 832000,China)

机构地区：[1]石河子大学医学院,新疆石河子832000

出　　处：《食品科学》2021年第5期208-214,共7页Food Science

基　　金：中国博士后科学基金项目(2017M613310XB);石河子大学校级科研项目(ZZZC20174A)。

摘　　要：目的:探讨槲皮素是否通过核因子E2相关因子2(nuclear factor erythroid 2-related factor 2,Nrf2)通路拮抗糖尿病大鼠胰腺氧化损伤。方法:选取SPF级SD大鼠48只,随机选取10只大鼠作为正常对照组,其余38只大鼠饲喂高脂饲料联合注射30 mg/kg mb链脲佐菌素建立2型糖尿病(type 2 diabetes mellitus,T2DM)模型。以大鼠随机血糖浓度不低于16.7 mmol/L作为造模成功判断标准,按血糖浓度分层将大鼠随机分为T2DM模型组、低剂量槲皮素(L-QU)、高剂量槲皮素(H-QU)干预组,每组10只,连续灌胃12周。测定大鼠胰腺组织匀浆液的氧化损伤和抗氧化指标,运用Western Blot、实时定量聚合酶链式反应测定Nrf2、血红素氧合酶1(heme oxygenase 1,HO-1)、谷胱甘肽硫转移酶(glutathione S-transferase,GST)、NADP(H):醌氧化还原酶1(NADP(H):quinone oxidoreductase 1,NQO1)蛋白及其mRNA表达量。结果:与T2DM模型组相比,低、高剂量槲皮素干预显著降低了大鼠血糖浓度和胰腺丙二醛含量(P<0.05),减轻胰岛素抵抗,显著提高超氧化物歧化酶等抗氧化酶活力(P<0.05),Nrf2以及下游抗氧化酶HO-1、NQO1的蛋白含量和mRNA表达量均显著上升(P<0.05)。结论:槲皮素可能是通过激活胰腺组织Nrf2信号通路,上调下游抗氧化酶表达,进而减轻T2DM大鼠胰腺氧化损伤,改善胰岛素抵抗,调节血糖水平,从而发挥防治糖尿病的作用。Objective:To investigate whether quercetin antagonizes oxidative pancreatic damage in diabetic rats through the nuclear factor erythroid 2-related factor 2(Nrf2)pathway.Methods:Forty-eight specific pathogen-free(SPF)Sprague-Dawley(SD)rats were selected for this study.Ten animals were randomly assigned to the control group and the remaining 38 rats were used to establish a model of type 2 diabetes mellitus(T2DM)by feeding a high-fat diet and simultaneously injecting streptozotocin(STZ)at a dose of 30 mg/kg mb.Random blood glucose no lower than 16.7 mmol/L was used as a criterion to confirm successful model establishment in 30 rats.According to glucose levels,the rats with T2DM were randomly divided into three equal groups(n=10):model,and low-and high-dose quercetin intervention.After continuous gavage for 12 weeks,the degree of oxidative damage and antioxidant indicators in pancreatic homogenate were evaluated.The protein and mRNA expression levels of Nrf2,heme oxygenase 1(HO-1),glutathione S-transferase(GST)and NADP(H):quinone oxido-reductase 1(NQO1)were measured by Western Blot and real-time fluorescence quantitative polymerase chain reaction.Results:Quercetin at both low and high doses could significantly reduce blood glucose levels and pancreatic malondialdehyde(MDA)content in T2DM rats(P<0.05),alleviate insulin resistance,increase the activity of antioxidant enzymes such as SOD(P<0.05),and up-regulate the protein and mRNA expression of Nrf2,HO-1 and NQO1(P<0.05).Conclusion:Quercetin may play a role in preventing and treating diabetes by activating the Nrf2 signaling pathway in pancreatic tissue and up-regulating the expression of downstream antioxidant enzymes to reduce oxidative damage,improve insulin resistance and regulate blood glucose levels.

关 键 词：糖尿病 抗氧化 降血糖作用 Nrf2信号通路 

分 类 号：R151.1[医药卫生—营养与食品卫生学]