运动和2,3,7,8-四氯二苯并二噁英(TCDD)持续暴露对大鼠肾脏氧化应激指标的影响

生态毒理学报
Asian Journal of Ecotoxicology
第18卷第2期2023年4月
V ol.18,No.2Apr.2023
㊀㊀基金项目:中央高校基本科研业务费(2017YB026);国家重点研发计划项目(2018YFC2000603)
㊀㊀第一作者:朱凤林(1991 ),女,硕士,研究方向为运动与健康㊁运动营养,E -mail:*****************㊀㊀*通信作者(Corresponding author ),E -mail:****************
DOI:10.7524/AJE.1673-5897.20220927002
朱凤林,闫会萍,陆一帆,等.运动和2,3,7,8-四氯二苯并二噁英(TCDD)持续暴露对大鼠肾脏氧化应激指标的影响[J].生态毒理学报,2023,18(2):366-372
Zhu F L,Yan H P,Lu Y F,et al.Effects of exercise and continuous exposure to 2,3,7,8-tetrachlorodibenzo -p -dioxin (TCDD)on renal oxidative stress in -dexes in rats [J].Asian Journal of Ecotoxicology,2023,18(2):366-372(in Chinese)
运动和2,3,7,8-四氯二苯并二噁英(TCDD )持续暴露对大鼠肾脏氧化应激指标的影响
朱凤林1,闫会萍2,*,陆一帆2,胡兵2,张弛2,翁凯翔2,王活活2
1.国家体育总局运动医学研究所,北京100029
2.北京体育大学运动医学与康复学院,北京100084收稿日期:2022-09-27㊀㊀录用日期:2022-12-02
摘要:观察8周有氧运动和2,3,7,8-四氯二苯并二噁英(2,3,7,8-tetrachlorodibenzo -p -dioxin,2,3,7,8-TCDD)持续暴露对大鼠肾脏组织氧化应激指标及相关蛋白水平的影响㊂选取40只8周龄雄性Sprague -Dawley(SD)大鼠,随机分为空白对照组(NC 组)㊁运动组(EC 组)㊁TCDD 暴露组(NT 组)和运动+TCDD 暴露组(ET 组),NT 组和ET 组进行8周TCDD 处理(腹腔注射,每周1次)首次剂量为6.4μg ㊃kg -1,第2~8周采用维持剂量(为首次剂量的21%),EC 组和ET 组采用游泳运动干预方式(5%体质量的尾部负重,每周5次)㊂8周干预后,测定血清尿素氮(urea nitrogen,BUN)㊁肌酐(creatinine,Cr),肾脏氧化应激相关指标脂质过氧化水平㊁谷胱甘肽(glutathione,GSH)㊁谷胱甘肽过氧化物酶(glutathione peroxidase,GSH -Px)㊁超氧化物歧化酶(superoxide dismutase,SOD)㊁过氧化氢酶(catalase,CAT)以及细胞色素P4501A1(cytochrome P4501A1,CYP1A1)蛋白含量㊂结果显示,运动可降低大鼠体质量和肾脏质量,提高GSH -Px 活性;TCDD 暴露可降低血清BUN 水平,提高脂质过氧化水平㊁GSH 含量㊁GSH -Px 和SOD 活性,提高CYP1A1蛋白含量;TCDD 暴露下运动可提高GSH -Px 活性,降低CYP1A1蛋白含量㊂本研究表明,TCDD 暴露可导致大鼠肾脏发生氧化应激,可能与TCDD 诱导的CYP1A1增加有关;8周中等强度有氧运动未能明显缓解TCDD 诱导的氧化应激,但能显著降低TCDD 诱导的CYP1A1水平,具体机制有待进一步研究㊂关键词:2,3,7,8-四氯二苯并二噁英;大鼠;氧化应激;运动
文章编号:1673-5897(2023)2-366-07㊀㊀中图分类号:X171.5㊀㊀文献标识码:A
Effects of Exercise and Continuous Exposure to 2,3,7,8-tetrachlorod-ibenzo-p -dioxin (TCDD )on Renal Oxidative Stress Indexes in Rats
Zhu Fenglin 1,Yan Huiping 2,*,Lu Yifan 2,Hu Bing 2,Zhang Chi 2,Weng Kaixiang 2,Wang Huohuo 2
1.National Institute of Sports Medicine,General Administration of Sport of China,Beijing 100029,China
2.School of Sport Medicine and Rehabilitation,Beijing Sport University,Beijing 100084,China
Received 27September 2022㊀㊀accepted 2December 2022
Abstract :This study aims to investigate the renal oxidative stress indexes and related protein levels in response to exercise and 2,3,7,8-tetrachlorodibenzo -p -dioxin (2,3,7,8-TCDD)exposure.Forty 8-week -old male Sprague -Dawley
第2期朱凤林等:运动和2,3,7,8-四氯二苯并二噁英(TCDD)持续暴露对大鼠肾脏氧化应激指标的影响367
㊀(SD)rats were randomly divided into blank control group(NC group),exercise group(EC group),TCDD exposure group(NT group)and exercise+TCDD exposure group(ET group).Both NT and ET groups were treated with TC-DD for8weeks(intraperitoneal injection,weekly).The initial dose was6.4μg㊃kg-1,followed by a maintenance dose(21%of the initial dose)from week2to8.Exercise intervention were prescribed for both EC and ET groups in the form of swimming(tail loading at5%of body weight,five times per week).After8weeks of intervention, serum urea nitrogen(BUN)and creatinine(Cr),indicators related to renal oxidative stress including lipid peroxida-tion level,glutathione(GSH),glutathione peroxidase(GSH-PX),superoxide dismutase(SOD),catalase(CAT)and cytochrome P4501A1(CYP1A1)protein relative content were measured.The results showed that exercise could re-duce body weight and kidney weight,and increase GSH-Px activity.TCDD exposure resulted serum BUN reduc-tion,and increased lipid peroxidation level,GSH content,GSH-Px and SOD activity,and CYP1A1level.The com-bination of exercise intervention and TCDD exposure can increase GSH-Px activity and decrease CYP1A1level. This study indicated that TCDD exposure can cause oxidative stress in rat kidneys,which may be related to the TCDD-induced increase of CYP1A1.Moderate-intensity aerobic exercise for8weeks could not significantly re-lieve TCDD-induced oxidative stress,but could significantly reduce the level of TCDD-induced CYP1A1.The spe-cific mechanism needs further research.
Keywords:2,3,7,8-TCDD;rat;oxidative stress;exercise
㊀㊀2,3,7,8-四氯二苯并二噁英(2,3,7,8-tetrachlorod-ibenzo-p-dioxin,2,3,7,8-TCDD)是一种持久性环境污染物,在环境中以复杂混合物的形式存在㊂研究表明,TCDD暴露会对机体产生严重的毒性效应,最常见的为氯痤疮㊁卟啉症和致癌性,此外还会损害肝脏㊁肾脏㊁生殖系统㊁中枢神经系统㊁免疫系统和内分泌系统[1-12]㊂TCDD通过与芳香烃受体(aryl hydro-carbon receptor,AhR)结合发挥作用并诱导细胞色素P450基因表达[13]㊂细胞色素P450活性增加的一个副产物是电子向分子氧转移的发生率增加,导致活性氧(reactive oxidative species,ROS)形成和脂质过氧化[14]㊂
一些动物实验研究观察到TCDD暴露与氧化应激增加相关的变化,包括超氧化物形成增加和脂质过氧化㊂Slezak等[15]的研究表明,小鼠急性和亚慢性TCDD暴露均会出现不同程度的氧化应激㊂此外,一些国内外文献也报道了TCDD暴露导致大鼠肾脏组织氧化应激指标的变化[4,16-18]㊂氧化应激参与多种肾病的发生发展过程,如通过破坏足细胞及肾Ⅳ型胶原蛋白进而损伤肾小球基底膜[19],促进IgA肾病(IgA nephropathy,IgAN)的疾病恶化[20],介导炎症反应引起肾小球通透性增加[21],损伤肾小球内皮细胞,促进慢性肾脏病(chronic kidney disease, CKD)的发病[22]㊂
运动训练是一个复杂的生物学过程,会引发细胞㊁组织/器官和各系统多层面的反应,有氧运动能带来诸多健康效益,包括改善心血管健康㊁促进心理
健康㊁防治2型糖尿病和延缓衰老等,但具体的分子
机制尚不明确[23-25]㊂研究表明,有氧运动可通过减轻心肌缺血后肾脏组织氧化应激水平和细胞凋亡,
起到缓解肾脏损伤的作用[26];另有研究表明,有氧运动可通过调控氧化应激相关的信号通路和蛋白表达,提高糖尿病大鼠抗氧化防御系统,降低脂质过氧化产物丙二醛(malondialdehyde,MDA)起到改善糖尿病大鼠肾脏损伤的作用[27-28]㊂
本研究基于前期建立的TCDD暴露模型[3],观察8周有氧运动和TCDD暴露对大鼠肾脏组织脂质过氧化水平㊁GSH含量和抗氧化酶(GSH-Px㊁SOD 和CAT)活性等氧化应激相关指标的影响,探究运动和TCDD暴露的交互效应,以期探讨机体在污染环境下进行运动的收益性并为运动促进机体健康的机制提供一定的理论依据㊂
1㊀材料与方法(Materials and methods)
1.1㊀对象及分组
实验选取40只8周龄Sprague-Dawley(SD)雄
性大鼠,清洁等级为SPF级,体质量为(282.95ʃ
16.61)g㊂购自北京维通利华实验动物技术有限公司(许可证编号:SCXK(京)2012-0001)㊂实验地点为北京体育大学中国健康研究院实验动物房,并已获得北京体育大学动物伦理委员会的批准,实验操作均符合规范,喂养饲料符合国家标准,分笼饲养大鼠,每笼5只,环境温度和湿度适宜,模拟昼夜光照
368
㊀生态毒理学报第18卷
节律㊂正式实验开始前一周进行适应性饲养和运动(3次无负重游泳训练)㊂适应期结束,将大鼠随机分为对照组(NC)㊁运动对照组(EC)㊁TCDD暴露组(NT)㊁运动+TCDD暴露组(ET),每组各10只㊂
1.2㊀实验设计方案
将TCDD(纯度>99.5%;Cambridge Isotope La-boratory,Ansover,MA,USA)溶于玉米油中,配制成浓度为6.4μg㊃kg-1的TCDD溶液,每采用腹腔注射方式,第1周的周三向TCDD干预组(NT组和ET 组)大鼠腹腔注射1mL上述浓度的TCDD溶液,第2周至第8周的周三注射维持剂量(为上述浓度的21%),第1周至第8周的每周三向NC组和EC组大鼠腹腔注射一次1mL的玉米油;与此同时,运动干预组(EC组和ET组)大鼠进行8周5%尾部负重游泳运动训练干预,根据每次下水游泳之前大鼠的体质量确定负重值,每周5次,每次30min㊂保持池温在合适温度,密切关注大鼠状态,防止溺水,并及时清理池水中排泄物,保持水质干净㊂
1.3㊀实验取材
运动和TCDD干预8周后取材,取材前禁食12 h㊂取材时,先称量并记录大鼠体质量,腹腔注射水合氯醛进行麻醉,分离腹主动脉取血;剥离大鼠肾脏,仔细剔除肾脏周围脂肪组织,然后用预冷的生理盐水浸洗干净,再用滤纸吸干水分,称重并记录㊂然后将肾脏剪成小块,用锡纸包裹好,速冻后存放于-80ħ冰箱待测㊂
1.4㊀指标测试
采用迈瑞Mindray全自动生化分析仪BS-820测定血清尿素氮(urea nitrogen,BUN)和血清肌酐(creatinine,Cr),采用比色法测试肾脏匀浆液中脂质过氧化水平㊁GSH含量㊁GSH-Px㊁SOD和CAT的活性,所用试剂盒购于北京华英生物技术研究所(中国北京);细胞色素P4501A1(cytochrome P4501A1, CYP1A1)抗体㊁细胞裂解液及免疫印迹(Western blot-ting)所需试剂购于天德悦生物科技公司(中国北京)㊂
1.5㊀统计方法
实验数据采用SPSS22.0软件进行统计分析,均以平均数ʃ标准差(meanʃSD)方式呈现㊂对大鼠血清和肾脏组织各指标结果进行正态性检验和方差齐性检验后,进行2ˑ2析因方差分析,显著性水平取P <0.05㊁P<0.01㊂
2㊀结果(Results)
2.1㊀有氧运动和TCDD暴露对大鼠体质量和肾脏质量的影响
结果显示(表1),运动对大鼠体质量有主效应(F =33.501,P=0.000,偏Eta方=0.504),对大鼠肾脏质量有主效应(F=11.720,P=0.002,偏Eta方=0.262),运动组大鼠体质量和肾脏质量明显下降;而运动对大鼠相对肾脏质量无主效应(P>0.05)㊂TCDD暴露对大鼠体质量㊁肾脏质量和相对肾脏质量无主效应(P>0.05)㊂运动和TCDD暴露对大鼠体质量㊁肾脏质量和相对肾脏质量均无交互效应(P>0.05)㊂2.2㊀有氧运动和TCDD暴露对大鼠血清指标的影响
由表2可知,运动对血清BUN和Cr均无主效应(P>0.05)㊂TCDD暴露对血清BUN有主效应(F= 7.812,P=0.009,偏Eta方=0.191),TCDD暴露降低BUN水平;对血清Cr无主效应(P>0.05)㊂运动和TCDD暴露对血清BUN和Cr的影响均无交互效应(P>0.05)㊂
2.3㊀有氧运动和TCDD暴露对大鼠肾脏氧化应激指标的影响
通过评估脂质过氧化水平和抗氧化状态来测定
表1㊀有氧运动和2,3,7,8-四氯二苯并二噁英(TCDD)暴露对大鼠体质量和肾脏质量的影响Table1㊀Effects of aerobic exercise and2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD)exposure
on body weight and kidney weight of rats
正常对照(NC) Normal control(NC)
运动对照组(EC)
Exercise control(EC)
TCDD暴露组(NT)
Normal toxic(NT)
运动+TCDD暴露组(ET)
Exercise toxic(ET)
体质量/g
Body weight/g
541.67ʃ44.61467.8ʃ21.02507.44ʃ26.33460.44ʃ31.16肾脏质量/g
Kidney weight/g
3.36ʃ0.38 2.99ʃ0.23 3.32ʃ0.29 3.07ʃ0.17肾脏质量/体质量
Relative kidney weight
0.62ʃ0.050.64ʃ0.050.65ʃ0.050.67ʃ0.06
第2期
朱凤林等:运动和2,3,7,8-四氯二苯并二噁英(TCDD)持续暴露对大鼠肾脏氧化应激指标的影响369
㊀TCDD 暴露导致的氧化应激,结果如图1所示㊂运动对肾脏GSH -Px 有主效应(F =8.135,P =0.007,偏Eta 方=0.198),运动使肾脏GSH -Px 活性升高;而对肾脏脂质过氧化水平㊁GSH 含量㊁SOD 和CAT 活性均无主效应(P >0.05)㊂
TCDD 暴露对肾脏脂质过氧化水平有可靠的主效应(F =11.304,P =0.002,偏Eta 方=0.255),对GSH 有主效应(F =94.234,P =0.000,偏Eta 方=0.734),对GSH -Px 有主效应(F =14.502,P =0.001,偏Eta 方=0.305),对SOD 有可靠的主效应(F =8.578,P =0.006,偏Eta 方=0.206),TCDD 暴露使肾脏脂质过氧化水平㊁GSH 含量㊁GSH -Px 和SOD 活性升高;而对CAT 无可靠的主效应(P >0.05)㊂
运动和TCDD 暴露对肾脏脂质过氧化水平㊁GSH 含量㊁抗氧化酶(GSH -Px ㊁SOD 和CAT)活性均无交互效应(P >0.05)㊂
2.4㊀有氧运动和TCDD 暴露对大鼠肾脏CYP1A1蛋白相对含量的影响
由图2可知,运动对肾脏CYP1A1无主效应(P >0.05);TCDD 暴露对肾脏CYP1A1有主效应(F =76.794,P =0.000,偏Eta 方=3.264),TCDD 暴露使CYP1A1蛋白含量增加;运动和TCDD 暴露对肾脏CYP1A1有交互效应(F =35.324,P =0.000,偏Eta 方=1.502),运动可下调TCDD 暴露引起的CYP1A1蛋白含量增加㊂3㊀讨论(Discussion )
血清中BUN 和Cr 水平升高可在一定程度上反映肾脏功能的损伤㊂研究表明,采用连续12d 的10μg ㊃kg -1的TCDD 灌胃处理[4]和连续3d 腹腔注射15μg ㊃kg -1的TCDD 的干预方式,均可造成大鼠肾
脏功能的损害,观察到血清BUN 和Cr 水平的显著
表2㊀有氧运动和TCDD 暴露大鼠血清尿素氮(BUN )和肌酐(Cr )的影响
Table 2㊀Effects of aerobic exercise and TCDD exposure on serum urea
nitrogen (BUN)and creatinine (Cr)in rats
正常对照(NC)Normal control (NC)
运动对照组(EC)Exercise control (EC)
TCDD 暴露组(NT)Normal toxic (NT)
运动+TCDD 暴露组(ET)Exercise toxic (ET)
BUN/(mmol ㊃L -1) 6.93ʃ0.927.01ʃ1.1 6.08ʃ0.95 6.2ʃ0.5Cr/(mmol ㊃L -1)
59.33ʃ3.68
60.24ʃ5.73
61.37ʃ2.94
58.46ʃ
2.76
图1㊀有氧运动和TCDD 暴露对大鼠肾脏氧化应激指标的影响
Fig.1㊀Effects of aerobic exercise and TCDD exposure on renal oxidative stress indexes in rats
370
㊀生态毒理学报第18
卷
图2㊀有氧运动和TCDD暴露对大鼠肾脏
CYP1A1蛋白相对含量的影响
注:**表示与NC组相比,P<0.01;##表示与NT组相比,P<0.01㊂Fig.2㊀Effects of aerobic exercise and TCDD exposure on renal CYP1A1protein relative content in rats Note:**represents P<0.01vs.NC;##represents P<0.01vs.NT.
升高[17-18]㊂本研究结果显示,NC组和EC组血清BUN分别为6.93mmol㊃L-1和7.01mmol㊃L-1,而TCDD暴露组(NT组和ET组)血清BUN分别为6.08mmol㊃L-1和6.2mmol㊃L-1,TCDD暴露对血清BUN有主效应,可降低BUN水平,但对血清Cr水平无主效应,说明持续8周首次剂量为6.4μg㊃kg-1的TCDD暴露方式尚未造成肾脏生理功能损害,其可能原因为本研究较上述研究采用的TCDD暴露剂量更小,频率更低㊂有研究发现,在同样的暴露方式下,大鼠肝脏发生明显肿大,肝功能指标活性升高,肝脏细胞出现炎症细胞浸润,表现出明显的肝脏毒性效应[29],而本实验中未观察到肾脏功能指标的明显升高,说明在首剂量为6.4μg㊃kg-1的TCDD暴露方式下,可能肾脏较肝脏具有更低的敏感性㊂Slezak等[15]通过对氧化应激指标的观察,也发现肝脏和肝外组织对TCDD暴露引起指标变化的敏感性和反应性存在差异㊂
当机体受到内在或外在刺激时,细胞抗氧化防御系统不足以清除代谢产生的ROS时,会导致脂质过氧化水平升高,出现氧化应激㊂本实验结果发现持续TCDD暴露后,大鼠肾脏组织脂质过氧化水平升高,抗氧化物质GSH含量增加㊁GSH-Px和SOD 酶活性增加㊂这与Lu等[4]的研究中将大鼠进行12 d的TCDD暴露后发现肾脏组织脂质过氧化产物MDA含量增加㊁抗氧化酶GSH-Px活性增加,机体出现氧化应激这一结论一致㊂研究表明抗氧化酶活性增加是机体抵抗氧化损伤的表现,是机体的代偿性适应[30],SOD活性的增加可能为细胞组织抵抗TCDD诱导的氧化应激提供了一种保护机制[31]㊂本研究观察到GSH和抗氧化酶水平升高,说明在首剂量为6.4μg㊃kg-1㊁持续8周外源性毒物TCDD的刺激下,激活了机体的代偿性保护机制,即积极调动抗氧化防御系统,生成更多的抗氧化物质消除TCDD 诱导产生的脂质过氧化㊁维持机体内部的氧化还原平衡状态,从而防止肾脏组织发生进一步氧化损伤㊂长期运动训练对机体来说是一种应激适应过程,长期运动后肌肉组织中的抗氧化酶活性增加,说明肌肉组织清除自由基能力增强,机体维持稳态的能力和适应性增强[32]㊂另有研究表明,长期有氧运动可降低大鼠心脏㊁肝脏等组织脂质过氧化水平,有效减轻氧化应激反应引起的组织损伤,是机体对应激反应适应性增强的表现[33]㊂本研究发现,运动对大鼠肾脏GSH-Px有主效应,可提升GSH-Px活性,但运动和TCDD暴露对大鼠肾脏脂质过氧化水平的影响无明显交互效应,说明8周的有氧运动可提升机体的抗氧化能力,但未能明显缓解TCDD诱导的氧化应激,这可能与运动对缓解TCDD诱导的脂质过氧化存在明显的时间效应[34]有关㊂提示在后续的研究中,可以通过增加不同干预时长的分组,观察氧化应激指标在不同时间点的变化趋势,探讨运动对TCDD诱导的氧化应激指标变化的影响㊂细胞色素P450是一类与氧化代谢活性有关的多基因家族酶类,由于它参与解除多种内源性㊁外源性化合物(包括致癌物质)以及代谢中间产物的毒性作用,因此是反应毒性效应的敏感指标㊂现有的研究普遍认为CYP1A1是参与TCDD发挥毒性的关键物质之一,TCDD暴露诱导Cyp1a1基因表达,提高CYP1A1蛋白水平,CYP1A1在催化毒物代谢过程中引起ROS生成增加,导致氧化还原状态失衡,进而发挥一系列毒性效应[13,35-36]㊂本研究发现TC-DD暴露导致大鼠肾脏CYP1A1蛋白含量显著升高,推测TCDD暴露导致大鼠肾脏发生氧化应激可能与TCDD诱导的CYP1A1增加有关㊂此外,本研究表明运动显著降低TCDD诱导的CYP1A1蛋白水平,可间接佐证前期研究[37]中运动能有效抵抗TCDD对肝脏组织CYP1A1和CYP1A2的诱导,从而减少其对7-乙氧基异吩恶唑酮脱乙基酶(7-ethoxyresorufin O-deethylase,EROD)㊁7-乙氧基香豆素-O-脱乙基酶(7-ethoxycou-marin O-deethylase, ECOD)活性的激活作用这一结论㊂目前,关于运动
第2期朱凤林等:运动和2,3,7,8-四氯二苯并二噁英(TCDD)持续暴露对大鼠肾脏氧化应激指标的影响371
㊀
影响TCDD等毒物代谢途径的研究鲜有报道,其具体分子机制有待进一步探究㊂
综上所述,首次剂量为6.4μg㊃kg-1的TCDD持续暴露可导致大鼠肾脏发生氧化应激,可能与TC-DD诱导的CYP1A1增加有关;8周中等强度有氧运动未能明显缓解TCDD诱导的氧化应激,但能降低TCDD诱导的CYP1A1水平,具体机制有待进一步研究㊂
通信作者简介:闫会萍(1975 ),女,博士,副研究员,主要研究方向为运动与健康㊂
参考文献(References):
[1]㊀Pohjanvirta R,Tuomisto J.Short-term toxicity of2,3,7,8-
tetrachlorodibenzo-p-dioxin in laboratory animals:Effects,
mechanisms,and animal models[J].Pharmacological Re-
views,1994,46(4):483-549
[2]㊀Hutin D,Long A S,Sugamori K,et al.2,3,7,8-tetrachlo-
rodibenzo-p-dioxin(TCDD)-inducible poly-ADP-ribose
polymerase(TIPARP/PARP7)catalytic mutant mice
(TiparpH532A)exhibit increased sensitivity to TCDD-in-
duced hepatotoxicity and lethality[J].Toxicological Sci-
ences,2021,183(1):154-169
[3]㊀闫会萍,宋小波,李飞霏,等.运动对2,3,7,8-四氯二苯
并二噁英持续暴露大鼠肝脏氧化应激的影响[J].生态
毒理学报,2017,12(2):81-87
Yan H P,Song X B,Li F F,et al.Effect of exercise on
liver redox status in continuously2,3,7,8-tetrachlorod-
ibenzo-p-dioxin(TCDD)-exposed rats[J].Asian Journal
of Ecotoxicology,2017,12(2):81-87(in Chinese)
[4]㊀Lu C F,Wang Y M,Peng S Q,et bined effects of
repeated administration of2,3,7,8-tetrachlorodibenzo-p-
dioxin and polychlorinated biphenyls on kidneys of male
rats[J].Archives of Environmental Contamination and
Toxicology,2009,57(4):767-776
[5]㊀朱凤林.运动对持续2,3,7,8-四氯二苯并二恶英(TCDD)
染毒大鼠肾毒性的影响[D].北京:北京体育大学,2018 Zhu F L.Effects of exercise on persistent2,3,7,8-tetra-
chlorodibenzo-p-dioxin-induced nephrotoxicity in rats
[D].Beijing:Beijing Sport University,2018(in Chinese)
[6]㊀Peterson R E,Theobald H M,Kimmel G L.Developmen-
tal and reproductive toxicity of dioxins and related com-
pounds:Cross-species comparisons[J].Critical Reviews
in Toxicology,1993,23(3):283-335
[7]㊀Gaspari L,Paris F,Kalfa N,et al.Experimental evidence
of2,3,7,8-tetrachlordibenzo-p-dioxin(TCDD)transgener-
ational effects on reproductive health[J].International
Journal of Molecular Sciences,2021,22(16):9091 [8]㊀Çiftçi O.Curcumin prevents toxic effects of2,3,7,8-tetra-
chlorodibenzo-p-dioxin(TCDD)on humoral immunity in
rats[J].Food and Agricultural Immunology,2011,22(1):
31-38
[9]㊀Li X Y,Li N,Han Y N,et al.2,3,7,8-tetrachlorodibenzo-
p-dioxin(TCDD)-induced suppression of immunity in
THP-1-derived macrophages and the possible mechanisms
[J].Environmental Pollution,2021,287:117302
[10]㊀Lu J,Liu M T,Fan Y,et al.TCDD induced lipid accumu-
lation by impairment of autophagic flux in THP-1macro-
phages[J].Environmental Science and Pollution Research
International,2021,28(27):36053-36059
[11]㊀Yue M S,Martin S E,Martin N R,et al.2,3,7,8-tetrachlo-
rodibenzo-p-dioxin exposure disrupts development of the
visceral and ocular vasculature[J].Aquatic Toxicology,
2021,234:105786
[12]㊀Wang H H,Wang J J,Zhu Y H,et al.Effects of different
intensity exercise on glucose metabolism and hepatic IRS/
PI3K/AKT pathway in SD rats exposed with TCDD[J].
International Journal of Environmental Research and Pub-
lic Health,2021,18(24):13141
[13]㊀Nebert D W,Roe A L,Dieter M Z,et al.Role of the aro-
matic hydrocarbon receptor and[Ah]gene battery in the
oxidative stress response,cell cycle control,and apoptosis
[J].Biochemical Pharmacology,2000,59(1):65-85 [14]㊀Goeptar A R,Scheerens H,Vermeulen N P.Oxygen and
xenobiotic reductase activities of cytochrome P450[J].
Critical Reviews in Toxicology,1995,25(1):25-65 [15]㊀Slezak B P,Hatch G E,DeVito M J,et al.Oxidative
stress in female B
6
C
3
F
1
mice following acute and sub-chronic exposure to2,3,7,8-tetrachlorodibenzo-p-dioxin
(TCDD)[J].Toxicological Sciences,2000,54(2):390-398 [16]㊀Ciftci O,Ozdemir I,Vardi N,et al.Ameliorating effects
of quercetin and chrysin on2,3,7,8-tetrachlorodibenzo-p-
dioxin-induced nephrotoxicity in rats[J].Toxicology and
Industrial Health,2012,28(10):947-954
[17]㊀Palaniswamy K S,Vishwanadha V P,Singaravelu S R.
Fish oil rich in eicosapentaenoic acid protects against oxi-
dative stress-related renal dysfunction induced by TCDD
in Wistar rats[J].Cell Stress and Chaperones,2014,19
(3):409-419
[18]㊀Vijaya Padma V,Kalai Selvi P,Sravani S.Protective
effect of ellagic acid against TCDD-induced renal oxida-
tive stress:Modulation of CYP1A1activity and antioxi-
dant defense mechanisms[J].Molecular Biology Reports,
2014,41(7):4223-4232
[19]㊀Takano T,Elimam H,Cybulsky A plement-media-
372
㊀生态毒理学报第18卷
ted cellular injury[J].Seminars in Nephrology,2013,33
(6):586-601
[20]㊀陈琛,刘书馨.IgA1异常糖基化与氧化应激在IgA肾
病发病机制中的研究进展[J].中国中西医结合肾病杂
志,2015,16(3):280-282
Chen C,Liu S X.Research progress of abnormal glycosy-
lation of IgA1and oxidative stress in the pathogenesis of
IgA nephropathy[J].Chinese Journal of Integrated Tradi-
tional and Western Nephrology,2015,16(3):280-282(in
Chinese)
[21]㊀Kuwabara A,Satoh M,Tomita N,et al.Deterioration of
glomerular endothelial surface layer induced by oxidative
stress is implicated in altered permeability of macromole-
cules in Zucker fatty rats[J].Diabetologia,2010,53(9):
2056-2065
[22]㊀Rhyu D Y,Yang Y Q,Ha H,et al.Role of reactive oxy-
gen species in TGF-beta1-induced mitogen-activated pro-
tein kinase activation and epithelial-mesenchymal transi-
tion in renal tubular epithelial cells[J].Journal of the A-
merican Society of Nephrology,2005,16(3):667-675 [23]㊀Galloza J,Castillo B,Micheo W.Benefits of exercise in
the older population[J].Physical Medicine and Rehabili-
tation Clinics of North America,2017,28(4):659-669 [24]㊀Smith P J,Merwin R M.The role of exercise in manage-
ment of mental health disorders:An integrative review[J].
Annual Review of Medicine,2021,72:45-62
[25]㊀Ruegsegger G N,Booth F W.Health benefits of exercise
[J].Cold Spring Harbor Perspectives in Medicine,2018,8
(7):a029694
[26]㊀Wu F N,Li Z,Cai M X,et al.Aerobic exercise alleviates
oxidative stress-induced apoptosis in kidneys of myocar-
dial infarction mice by inhibiting ALCAT1and activating
FNDC5/Irisin signaling pathway[J].Free Radical Biology
&Medicine,2020,158:171-180
[27]㊀何黛,侯改霞.有氧运动对糖尿病肾病大鼠肾功能影
响研究[J].北京体育大学学报,2009,32(12):66-68
He D,Hou G X.The effect of aerobic exercises to im-
prove diabetic kidney function of rats[J].Journal of Bei-
jing Sport University,2009,32(12):66-68(in Chinese) [28]㊀孟艳,林文弢,徐国琴,等.不同强度的耐力运动对糖
尿病大鼠肾脏氧化应激与TIMP-1表达的影响[J].山
东体育学院学报,2011,27(9):51-55
Meng Y,Lin W T,Xu G Q,et al.Effects of different in-
tensity endurance exercise on renal oxidative stress and
the expression of tissue inhibitor of metalloproteinase-1in
diabetic rats[J].Journal of Shandong Institute of Physical
Education and Sports,2011,27(9):51-55(in Chinese) [29]㊀张弛.运动对TCDD染毒大鼠肝脏Nrf2及相关蛋白表
达的影响[D].北京:北京体育大学,2017
Zhang C.Effects of exercise on the expression of liver
Nrf2and related protein[D].Beijing:Beijing Sport Uni-
versity,2017(in Chinese)
[30]㊀卢咏才,王淑华,刘小青,等.高脂血症㊁脂质过氧化㊁
抗氧化酶活性与动脉粥样硬化的关系[J].中国病理生
理杂志,1993,9(3):391-396
Lu Y C,Wang S H,Liu X Q,et al.The relation of hyper-
lipidemia,lipid peroxidation,anti-oxidative enzyme activi-
ty to atherosclerosis[J].Chinese Journal of Pathophysiol-
ogy,1993,9(3):391-396(in Chinese)
[31]㊀Kern P A,Fishman R B,Song W,et al.The effect of2,3,
7,8-tetrachlorodibenzo-p-dioxin(TCDD)on oxidative en-
zymes in adipocytes and liver[J].Toxicology,2002,171
(2-3):117-125
[32]㊀陈瑗,周玫.自由基与衰老[M].北京:人民卫生出版社,
2004:8-10
[33]㊀Farhat F,Dupas J,Amérand A,et al.Effect of exercise train-
ing on oxidative stress and mitochondrial function in rat
heart and gastrocnemius muscle[J].Redox Report:Commu-
nications in Free Radical Research,2015,20(2):60-68 [34]㊀闫会萍,赵伟,白玉茗,等.运动对2,3,7,8-四氯二苯并
二噁英大鼠血清超氧化物歧化酶㊁丙二醛水平的影响
[J].浙江体育科学,2017,39(4):95-98
Yan H P,Zhao W,Bai Y M,et al.The effect of exercise
on the changes of serum SOD and MDA in2,3,7,8-tetra-
chlorodibenzo-p-dioxin exposed rates[J].Zhejiang Sport
Science,2017,39(4):95-98(in Chinese)
[35]㊀Baba T,Mimura J,Nakamura N,et al.Intrinsic function
of the aryl hydrocarbon(dioxin)receptor as a key factor
in female reproduction[J].Molecular and Cellular Biolo-
gy,2005,25(22):10040-10051
[36]㊀Knerr S,Schaefer J,Both S,et al.2,3,7,8-tetrachlorod-
ibenzo-p-dioxin induced cytochrome P450s alter the for-
mation of reactive oxygen species in liver cells[J].Molec-
ular Nutrition&Food Research,2006,50(4-5):378-384 [37]㊀闫会萍,张弛,杜乐,等.运动对急性暴露于2,3,7,8-四
氯二苯并二噁英大鼠肝组织酶活性的影响[J].生态毒
理学报,2015,10(2):204-209
Yan H P,Zhang C,Du L,et al.The effect of exercise on
the activity of liver microsomal oxidase in2,3,7,8-tetra-
chlorodibenzo-p-dioxin(TCDD)-exposed rats[J].Asian
Journal of Ecotoxicology,2015,10(2):204-209(in Chi-
nese)Ң。