文献类型：期刊文献

中文题名：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

英文题名：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[2];张静[3];周绮云[3];秦菲[3]

机构：[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

第一机构：北京联合大学

年份：2025

卷号：46

期号：8

起止页码：362-370

中文期刊名：食品工业科技

外文期刊名：Science and Technology of Food Industry

收录：;EI(收录号：20251518227303);北大核心:【北大核心2023】；

基金：北京市教育委员会科技计划项目(KM202211417004)。

语种：中文

中文关键词：白藜芦醇;运动性肾损伤;大鼠;Keap1-Nrf2;信号通路;细胞凋亡;本文网刊:

外文关键词：resveratrol;exercise-induced kidney injury;rat;kelch-like ECH-associated protein-1(Keap1)-nuclear factorE2-related factor 2(Nrf2)signaling pathway;apoptosis

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 mRNA和蛋白质表达水平,SOD、CAT和GSH-ST活性,p-Nrf2和Bcl-2蛋白质表达水平及p-Nrf2/Nrf2比值均显著下降(P<0.01)。经4周白藜芦醇干预,与EIKIM组大鼠比较,REIKIM组大鼠肾组织病理改变有效改善;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、Caspase-3蛋白质表达水平,以及Bax/Bcl-2比值均显著下降(P<0.05或P<0.01);肾组织中Nrf2、NQO1、HO-1 mRNA和蛋白质表达水平,SOD、CAT和GSH-ST活性,pNrf2和Bcl-2蛋白质表达水平及p-Nrf2/Nrf2比值均显著升高(P<0.05或P<0.01)。结论:白藜芦醇可有效激活大强度运动大鼠肾组织中Keap1-Nrf2信号通路,抑制氧化应激和细胞凋亡,保护肾结构和功能完整性。
Objective: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 protein expression and p-Nrf2/Nrf2 ratio(P<0.01).In contrast,after 4 weeks of resveratrol treatment,rats in group REIKIM exhibited significant improvements in renal pathology compared to group EIKIM,with decreased 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<0.05 or P<0.01),and increased levels of renal Nrf2,NQO1,HO-1 mRNA and protein expression,SOD,CAT and GSH-ST activity,p-Nrf2,Bcl-2 protein expression and p-Nrf2/Nrf2 ratio(P<0.05 or P<0.01).Conclusions:Resveratrol can activate the Keap1-Nrf2 signaling pathway of rats subjected to high-intensity exercise effectively,suppress oxidative stress and apoptosis,thereby protecting the integrity of renal structure and function.