白藜芦醇调控Keap1-Nrf2信号通路对大鼠运动性肾损伤的保护作用  

Protective Effect of Resveratrol on Exercise-induced Kidney Injury in Rats by Regulating Keap1-Nrf2 Signaling Pathway

作　　者：周海涛[1] 胡戈 张静[3] 周绮云[3] 秦菲[3] ZHOU Haitao;HU Ge;ZHANG Jing;ZHOU Qiyun;QIN Fei(Institute of Physical Exercise and Health,Beijing Union University,Beijing 100101,China;School of Physical Education,Changzhou University,Changzhou 213164,China;College of Biochemical Engineering,Beijing Union University,Beijing 100023,China)

机构地区：[1]北京联合大学体育运动与健康研究所,北京100101 [2]常州大学体育学院,江苏常州213164 [3]北京联合大学生物化学工程学院,北京100023

出　　处：《食品工业科技》2025年第8期362-370,共9页Science and Technology of Food Industry

基　　金：北京市教育委员会科技计划项目(KM202211417004)。

摘　　要：目的:探究白藜芦醇对大鼠运动性肾损伤的保护机制。方法:32只7周龄SPF级雄性SD大鼠随机分为安静组(CONT组,8只)、白藜芦醇组(RESV组,8只)、运动性肾损伤模型组(EIKIM组,8只)和白藜芦醇干预的运动性肾损伤模型组(REIKIM组,8只)。EIKIM和REIKIM组大鼠进行跑台训练建立运动性肾损伤模型。4周训练期间,RESV、REIKIM组大鼠在每次训练前1 h根据体重给予剂量和体积分别为150 mg/kg·bw和5 mL/kg的白藜芦醇溶液灌胃,其余大鼠给予等体积溶剂灌胃。末次训练24 h后采集各组大鼠血液和肾样本。通过HE染色评估大鼠肾组织形态。测定大鼠血液中肌酐(creatinine,Cr)和尿素氮(urea nitrogen,UN)水平及肾组织中Kelch样环氧氯丙烷相关蛋白-1(kelch-like ECH-associated protein-1,Keap1)、核因子E2相关因子2(nuclear factor-E2-related factor 2,Nrf2)、NAD(P)H醌脱氢酶1(NAD(P)H:quinone oxidoreductase 1,NQO1)、血红素氧合酶1(heme oxygenase-1,HO-1)mRNA和蛋白质表达水平,磷酸化(phosphorylated nuclear factor erythroid 2-related factor 2,p-Nrf2)蛋白质表达水平,超氧化物歧化酶(superoxide dismutase,SOD)、过氧化氢酶(catalase,CAT)和谷胱甘肽S移换酶(glutathione S-transferase,GSH-ST)活性,丙二醛(malondialdehyde,MDA)和活性氧簇(reactive oxygen species,ROS)含量,细胞凋亡及B淋巴细胞瘤因子-2(B cell lymphoma-2 protein,Bcl-2)、Bcl-2相关X蛋白(bcl-2-associated X protein,Bax)、含半胱氨酸的天冬氨酸蛋白水解酶9(cysteinyl aspartate specific proteinase-9,Caspase-9)、含半胱氨酸的天冬氨酸蛋白水解酶-3(cysteinyl aspartate specific proteinase-3,Caspase-3)蛋白质表达水平。结果:经4周大强度跑台训练,与CONT组大鼠比较,EIKIM组大鼠肾组织病理改变明显;血液中Cr和UN水平,肾组织中Keap1 mRNA和蛋白质表达水平,MDA和ROS含量,细胞凋亡及Bax、Caspase-9和Caspase-3蛋白质表达水平,以及Bax/Bcl-2比值均显著升高(P<0.01);肾组织中Nrf2、NQO1、HO-1 mRNAObjective:To investigate the protective mechanism of resveratrol on exercise-induced kidney injury in rats.Methods:Thirty-two 7-week-old SPF-grade male SD rats were randomly assigned to four groups:control group(CONT,n=8),resveratrol group(RESV,n=8),exercise-induced kidney injury model group(EIKIM,n=8),and resveratrol-treated exercise-induced kidney injury group(REIKIM,n=8).Rats in groups EIKIM and REIKIM underwent high-intensity treadmill training to establish a model of exercise-induced kidney injury.During the four-week training,rats in groups RESV and REIKIM were administered resveratrol solution intragastrically at a dosage of 150 mg/kg·bw and a volume of 5 mL/kg,1 h prior to each training session,and the remaining rats received an equal volume of solvent.Blood and kidney samples were obtained 24 h post the final training session.Kidney morphology was assessed using HE staining.Levels of serum creatinine(Cr)and urea nitrogen(UN),renal kelch-like ECH-associated protein-1(Keap1),nuclear factor-E2-related factor 2(Nrf2),NAD(P)H:quinone oxidoreductase 1(NQO1),heme oxygenase-1(HO-1)mRNA and protein expression levels,phosphorylated nuclear factor erythroid 2-related factor 2(p-Nrf2)protein expression level,activities of superoxide dismutase(SOD),catalase(CAT)and glutathione S-transferase(GSH-ST)activity,levels of malondialdehyde(MDA),reactive oxygen species(ROS),apoptosis,B cell lymphoma-2 protein(Bcl-2),bcl-2-associated X protein(Bax),cysteinyl aspartate specific proteinase-9(Caspase-9),and cysteinyl aspartate specific proteinase-3(Caspase-3)protein expression were detected.Results:After 4 weeks of high-intensity treadmill training,significant renal pathological changes of rats were observed in group EIKIM compared to group CONT,with increased levels of serum Cr and UN,renal Keap1 mRNA and protein expression,MDA,ROS,apoptosis,Bax,Caspase-9,Caspase-3 protein expression and Bax/Bcl-2 ratio(P<0.01),and decreased levels of renal Nrf2,NQO1,HO-1 mRNA and protein expression,SOD CAT and GSH-ST activity,p-Nrf2,Bcl-2 prot

关 键 词：白藜芦醇 运动性肾损伤 大鼠 Keap1-Nrf2信号通路 细胞凋亡 

分 类 号：TS201.4[轻工技术与工程—食品科学]