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运动对二噁英致大鼠脂质合成代谢障碍的干预作用及其机制研究
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摘要
目的:本研究以SD大鼠为研究对象,研究运动、二噁英对大鼠肝脏脂质合成代谢的影响,探讨其影响机制,以此来改变人类对代谢性疾病发病机制的新认识,并为运动锻炼防治二噁英环境污染物引起代谢性疾病提供相应理论支持。方法:选取8周龄雄性SD大鼠随机分为对照组(C)、运动组(E)、染毒组(T)、运动染毒组(ET)。T、ET组大鼠腹腔注射首剂量6.4μg/kg·bw的2,3,7,8-TCDD,之后每隔1w给予上述剂量的21%持续染毒,连续7w。E、ET组大鼠尾部负重(5%bw)进行游泳运动,每周5天,每次30分钟。每日观察大鼠健康状况,给药后第1、3、4、6、8w末内眦静脉取血检测血脂指标,第4、8w末分别处死半数动物,计算脏器相对重量,取肝脏组织行生化指标、组织病理学检测,实时荧光定量PCR、 Western Blot检测ACC1、FAS、SCD1、LXRa、SREBP-1、ChREBP mRNA及蛋白表达。
     结果:1、各组大鼠精神状态良好,活动能力正常;体重呈增长趋势,但每组趋势不同;ET、T组肝脏相对重量显著增高;4w末ET组附睾脂肪相对重量显著下降。2、2,3,7,8-TCDD可显著增高肝脏TG含量,长期运动可显著降低肝脏TG含量;各组大鼠中E组血清TG、TC含量最低,ET、T组血清TG、TC呈增长趋势;ET、T组血清LDL-C显著增高,长期运动E组血清HDL-C显著增高。3、肝脏组织HE和油红0染色显示2,3,7,8-TCDD可诱发明显病理性改变及脂质浸润,长期运动可改善病理性改变及脂质浸润情况。4、2,3,7,8-TCDD持续染毒可显著增加脂质合成代谢过程中相关酶ACC1、FAS、SCD1及转录因子LXRa、SREBP-1的mRNA和蛋白表达,长期运动可显著降低染毒大鼠ACC1、FAS、SCD1、LXRa、SREBP-1的mRNA和蛋白表达,2,3,7,8-TCDD染毒和运动对某些指标的影响存在交互作用,表明运动有干预效应。
     结论:1、2,3,7,8-TCDD影响肝脏脂质合成代谢过程中相关酶及转录因子的mRNA和蛋白表达,从而造成脂质代谢紊乱。2、运动对肝脏脂质合成代谢的影响具有时间效应,长期运动才明显体现,其具体影响机制还需进一步研究。3、长期运动可改善2,3,7,8-TCDD造成脂质代谢的紊乱。
Objective:This paper investigated the effects of exercise and2,3,7,8-TCDD on the hepatic lipid anabolic in the SD rats, and explored the mechanism of the effects. The aim is to develop a new knowledge of the pathogenesis of metabolic diseases, and provide a corresponding support for the hypothesis that exercise might prevent the metabolic deseases caused by dioxin-like environmental pollutants.
     Methods:SD rats (8weeks old) were divided into4different groups randomly:control group (C), exercise group (E), T group treated with2,3,7,8-TCDD, and ET group treated with exercise and2,3,7,8-TCDD. Rats in groups T and ET were intraperitoneally given2,3,7,8-TCDD in a first dose of6.4μg/kg·bw, and thereafter, they were administrated a mantenance dosage by21%of the first dose weekly for7weeks. Groups E and ET swam30min every day with a tail load of5%body weight for5days per week. The healthy status of the rats was daily observed. The blood samples were collected through the inner canthus vein at the end of1st,3rd,4th,6th,8th weekends, and then the serum lipid indicators were measured. Half groups of the rats were killed at the4th and8th weekends respectively, and the relative weights of the organs were calculated. The liver tissues were collected to conduct the biochemical parameter measurements and histopathological detections. ACC1, FAS, SCD1, LXRa, SREBP-1, ChREBP mRNA and protein expression were determined via real-time quantitative PCR and Western Blot methods.
     Results:(1) All rats were in good mental state and normal activity. And the body weights showed a growth trend, but there were differences between each group. The relative weights of the livers significantly increased in the rats of groups ET and T. The relative weights of epididymal fat greatly decreased at the4th weekend in the rats of group ET.(2)2,3,7,8-TCDD showed a significantly increasing effect on the TG concentrations in livers, while long-term exercise might have a deceasing effect. Rats in group E had the lowest serum TG and TC concentrations, while that of rats in groups ET and T showed a increasing trend. The serum concentrations of LDL-C significantly increased in rats of groups ET and T, but the serum HDL-C concentraions of rats in group E increased.(3) Results of HE and Oil Red0staining of the liver tissues demonstrated that2,3,7,8-TCDD may induce obvious pathological changes and lipid infiltration, which can be improved by long-term exercise.(4) Continuous exposure to2,3,7,8-TCDD may significantly increase mRNA and protein expression of enzymes (ACC1, FAS, SCD1) and transcription factors (LXRa, SREBP-1) related to the lipid synthesis. Long-term exercise may significantly decrease the above mRNA and protein expressions. The interactions in some indicators between2,3,7,8-TCDD exposure and exercise treatment showed an antagonistic effect.
     Conclusions:(1)2,3,7,8-TCDD may effect on the mRNA and protein expression of the hepatic lipid anabolic related enzymes and transcription factors, and consequently result in the lipid metabolism disorders.(2) The influences of exercise on hepatic lipid anabolic showed a time effect, indicated that only long-term exercise might have an evident effect. However, further studies should be conducted to investigate the mechanism.(3) Long-term exercise can improve the lipid metabolic disorders caused by2,3,7,8-TCDD.
引文
[1]Birnbaum L S. Developmental effects of dioxins and related endocrine disrupting chemicals [J]. Toxicology letters,1995,82:743-750.
    [2]Cranmer M, Louie S, Kennedy R H, et al. Exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) is associated with hyperinsulinemia and insulin resistance[J]. Toxicological sciences, 2000,56(2):431-436.
    [3]Lee D, Lee I, Song K, et al. A Strong Dose-Response Relation Between Serum Concentrations of Persistent Organic Pollutants and Diabetes Results from the National Health and Examination Survey 1999-2002[J]. Diabetes care,2006,29(7):1638-1644.
    [4]Hokanson R, Miller S, Hennessey M, et al. Disruption of estrogen-regulated gene expression by dioxin:downregulation of a gene associated with the onset of non-insulin-dependent diabetes mellitus (type 2 diabetes)[J]. Human & experimental toxicology,2004,23(12):555-564.
    [5]Longnecker M P, Michalek J E. Serum dioxin level in relation to diabetes mellitus among Air Force veterans with background levels of exposure[J]. Epidemiology,2000,11(1):44-48.
    [6]Carpenter D O. Environmental contaminants as risk factors for developing diabetes[J]. Reviews on environmental health,2011,23(1):59-74.
    [7]Henriksen G L, Ketchum N S, Michalek J E, et al. Serum dioxin and diabetes mellitus in veterans of Operation Ranch Hand[J]. Epidemiology,1997:252-258.
    [8]Emond C, Birnbaum L S, Devito M J. Use of a physiologically based phannacokinetic model for rats to study the influence of body fat mass and induction of CYP1A2 on the pharmacokinetics of TCDD[J]. Environmental health perspectives,2006,114(9):1394.
    [9]Pelclova D, Fenclova Z, Preiss J, et al. Lipid metabolism and neuropsychological follow-up study of workers exposed to 2,3,7,8-tetrachlordibenzo-p-dioxin[J]. International archives of occupational and environmental health,2002,75:60-66.
    [10]焦守海.2,3,7,8-四氯苯并二恶英(TCDD)对高脂喂养大鼠糖代谢和脂代谢影响研究[D].济南大学,2011.
    [11]Alcock R E, Mclachlan M S, Johnston A E, et al. Evidence for the presence of PCDD/Fs in the environment prior to 1900 and further studies on their temporal trends[J]. Environmental science & technology,1998,32(11):1580-1587.
    [12]Nestrick T J, Lamparski L L. Isomer-specific determination of chlorinated dioxins for assessment of formation and potential environmental emission from wood combustion[J]. Analytical chemistry,1982,54(13):2292-2299.
    [13]Sheffield A. Sources and releases of PCDD's and PCDF's to the Canadian environment[J]. Chemosphere,1985,14(6):811-814.
    [14]包志成,张尊.三氯苯生产残渣中PCDDs和PCDFs的分析[J].环境化学,1989,8(4):6-9.
    [15]张庆华,吴文忠,占伟,等.”永固紫”染料和四氯苯醌中多氯代二苯并二(口恶)(口英)/呋喃的分析[J].色谱,2000,18(1).
    [16]王志芳,丁琼,王开祥,等.我国典型非木浆造纸二嗯英排放研究[J].环境科学,2012,33(002):574-579.
    [17]Kim K, Hong K, Ko Y, et al. Emission characteristics of PCDD/Fs in diesel engine with variable load rate[J]. Chemosphere,2003,53(6):601-607.
    [18]Gullett B K, Ryan J V. On-road emissions of PCDDs and PCDFs from heavy duty diesel vehicles[J]. Environmental science & technology,2002,36(13):3036-3040.
    [19]Geueke K, Gessner A, Quass U, et al. PCDD/F emissions from heavy duty vehicle diesel engines[J]. Chemosphere,1999,38(12):2791-2806.
    [20]韩伟,张芃.暴露于二恶英工人氯痤疮发病情况及尿ALA含量调查[J].化工劳动保护.工业卫生与职业病分册,1995,6.
    [21]Coenraads P J, Olie K, Tang N J. Blood lipid concentrations of dioxins and dibenzofurans causing chloracne[J]. British journal of dermatology,1999,141:694-697.
    [22]Geusau A, Abraham K, Geissler K, et al. Severe 2,3,7,8-tetrachlorodibenzo-p-dioxin (TCDD) intoxication:clinical and laboratory effects.[J]. Environmental health perspectives,2001, 109(8):865.
    [23]Park S, Yoon W, Son H, et al. Effects of 2,3,7,8-tetrachlorodibenzo-p-dioxin on leukocyte function-associated antigen-1 mediated splenocyte adhesion[J]. Anticancer research,2006,26(6B): 4575-4583.
    [24]Suh J, Jeon Y J, Kim H M, et al. Aryl hydrocarbon receptor-dependent inhibition of AP-1 activity by 2,3,7,8-tetrachlorodibenzo-p-dioxin in activated B cells[J]. Toxicol Appl Pharmacol, 2002,181(2):116-123.
    [25]Valdez K E, Shi Z, Ting A Y, et al. Effect of chronic exposure to the aryl hydrocarbon receptor agonist 2,3,7,8-tetrachlorodibenzo-p-dioxin in female rats on ovarian gene expression[J]. Reprod Toxicol,2009,28(1):32-37.
    [26]Tonn T, Esser C, Schneider E M, et al. Persistence of decreased T-helper cell function in industrial workers 20 years after exposure to 2,3,7,8-tetrachlorodibenzo-p-dioxin.[J]. Environmental health perspectives,1996,104(4):422.
    [27]许振成,许虹,张素坤,等.2,3,7,8-四氯二苯并对二嗯英对大鼠卵巢颗粒细胞雌二醇和孕酮分泌的影响[J].生态毒理学报,2009,4(1):131-135.
    [28]沈杨,刘娟,任慕兰.二噁英对小鼠异位子宫内膜影响的分子机制研究[J].中山大学学报:医学科学版,2010,31(005):608-613.
    [29]方庆仙,张信美,林俊.二嗯英对子宫内膜异位症患者子宫内膜细胞’TNF-a表达的影响[J].生殖与避孕,2011,31(7):449-454.
    [30]刘静,汤乃军,赵力军,等.亚慢性染毒2,3,7,8-四氯二苯并二嗯英对雄性大鼠生殖系统的影响[J].中国工业医学杂志,2006,19(4):196-198.
    [31]黄莉,戴丽军,叶炳飞,等.2,3,7,8-四氯苯二嗯英对NIH小鼠胚胎发育的影响[J].中国比较医学杂志,2005,15(3):150-153.
    [32]Mocarelli P, Gerthoux P M, Ferrari E, et al. Paternal concentrations of dioxin and sex ratio of offspring[J]. The Lancet,2000,355(9218):1858-1863.
    [33]甘立强.2,3,7,8-四氯二苯二噁英与先天性腭裂发病相关性及其机制研究[D].重庆医科大学,2010.
    [34]刘明学.2,3,7,8-四氯二苯并二嗯英所致先天性肾积水的发生机制及其预防的实验研究[D].重庆医科大学,2009.
    [35]Rogan W J, Gladen B C, Hung K, et al. Congenital poisoning by polychlorinated biphenyls and their contaminants in Taiwan.[J]. Science (New York, NY),1988,241(4863):334.
    [36]Pesatori A C, Consonni D, Bachetti S, et al. Short-and Long-Term Morbidity and Mortality in the Population Exposed to Dioxin after the" Seveso Accident"[J]. Industrial health,2003,41(3): 127-138.
    [37]Katsoyiannis A, Gioia R, Sweetman A J, et al. Continuous monitoring of PCDD/Fs in the UK atmosphere:1991-2008[J]. Environmental science & technology,2010,44(15):5735-5740.
    [38]Hiester E, Bohm R, Eynck P, et al. Long term monitoring of PCDD, PCDF and PCB in bulk deposition samples[J]. Organohalogen Compounds,1993,12:147-150.
    [39]Abad E, Martinez K., Gustems L, et al. Ten years measuring PCDDs/PCDFs in ambient air in Catalonia (Spain)[J]. Chemosphere,2007,67(9):1709-1714.
    [40]Summary of Ambient Dioxin Level in Hong Kong[EB/OL]. http://www.epd-asg.gov.hk/englisli/report/dioxin.html.
    [41]余莉萍.广州大气中二噁英的浓度分布和几种典型二噁英排放源的初步研究[D].中国科学院广州地球化学研究所,2007.
    [42]应媛媛.上海市典型区域大气和土壤样品中二嗯英初探[D].华东理工大学,2010.
    [43]孙俊玲.北京市大气环境中二嗯英和多氯联苯的污染特征和气-粒分配行为研究[D].中国地质大学(北京),2009.
    [44]巩宏平,刘劲松,潘荷芳,等.杭州市环境空气中二嗯英类物质检测与分析[J].环境监测管理与技术,2012,24(2):27-30.
    [45]张素坤.珠江三角洲地区土壤/沉积物中PCDDs和PCDFs的空间分布和污染源研究[D].中国科学院广州地球化学研究所,2006.
    [46]Maystrenko V, Kruglov E, Amirova Z, et al. Polychlorinated dioxin and dibenzofuran levels in the environment and food from the Republic of Bashkortostan, Russia[J]. Chemosphere,1998, 37(9):1699-1708.
    [47]Rotard W, Christmann W, Knoth W. Background levels of PCDD/F in soils of Germany[J]. Chemosphere,1994,29(9):2193-2200.
    [48]李常清,陈左生,李伟,等.土壤中的二恶英类物质污染及其污染源[J].地球与环境,2004,32(2):63-69.
    [49]邓芸芸,贾丽娟,殷浩文.上海地区土壤二噁英污染状况调查[J].环境与职业医学,2008,25(4):353-355,359.
    [50]杨志军,倪余文,张青,等.上海市和大连市大气气溶胶和土壤样品中的二噁英初探[J].广州环境科学,2004(1):25-27.
    [51]岳建华.长株潭城市群二噁英污染水平初探[J].广州化工,2011(24):106-109.
    [52]周志广,田洪海,刘爱民,等.北京市农业区不同使用类型土壤中二噁英类分析[J].环境化学,2010(1):18-24.
    [53]Hilscherova K, Kannan K, Nakata H, et al. Polychlorinated dibenzo-p-dioxin and dibenzofuran concentration profiles in sediments and flood-plain soils of the Tittabawassee River, Michigan[J]. Environmental science & technology,2003,37(3):468-474.
    [54]Dalla Valle M, Marcomini A, Jones K C, et al. Reconstruction of historical trends of PCDD/Fs and PCBs in the Venice Lagoon, Italy[J]. Environment international,2005,31(7): 1047-1052.
    [55]吴文忠,徐盈,张甬元,等.鸭儿湖地区多氯代二苯并二噁/呋喃(PCDD/F)的污染状况及其来源归宿的初步研究[J].环境科学学报,1998,18(4):415-420.
    [56]Zheng M, Bao Z, Wang K, et al. Polychlorinated dibenzo-p-dioxins and dibenzofurans in lake sediments from Chinese schistosomiasis areas [J]. Bulletin of environmental contamination and toxicology,1997,59(4):653-656.
    [57]陈济安,罗教华,黄玉晶,等.三峡库区水中二噁英类物质污染现状研究[C].北京:2007.
    [58]杨永亮,史双昕,潘静,等.南四湖沉积物中二(口恶)英类化合物的分布[J].环境化学,2004,23(5):549-555.
    [59]杨敏.辽河流域沉积物中持久性有机污染物的研究[D].中国科学院大连化学物理研究所,2006.
    [60]张庆华.太湖和海河流域天津段二恶英类化合物污染特征的研究[D].中国科学院生态环境研究中心,2004.
    [61]潘静.典型东部沿海和西部高原地区持久性有机污染物的污染特征研究[D].东华大学,2008.
    [62]Kim B, Lee S, Kim H, et al. Determination of polychlorinated dibenzo-p-dioxins and dibenzofurans and comparison of extraction methods for edible freshwater fish and frogs in South Korea by using a high-resolution GC/MS[J]. Food additives and contaminants,2004,21(7): 700-710.
    [63]Kuehl D W, Butterworth B, Marquis P J. A national study of chemical residues in fish:III: Study results[J]. Chemosphere,1994,29(3):523-535.
    [64]Chovancova J, Kocan A, Jursa S. PCDDs, PCDFs and dioxin-like PCBs in food of animal origin (Slovakia).[J]. Chemosphere,2005,61(9):1305.
    [65]Loutfy N, Fuerhacker M, Tundo P, et al. Monitoring of polychlorinated dibenzo-p-dioxins and dibenzofurans, dioxin-like PCBs and polycyclic aromatic hydrocarbons in food and feed samples from Ismailia city, Egypt[J]. Chemosphere,2007,66(10):1962-1970.
    [66]Gomara B, Bordajandi L R, Fernandez M A, et al. Levels and trends of polychlorinated dibenzo-p-dioxins/furans (PCDD/Fs) and dioxin-like polychlorinated biphenyls (PCBs) in Spanish commercial fish and shellfish products,1995-2003[J]. Journal of agricultural and food chemistry,2005,53(21):8406-8413.
    [67]Fernandes A, Mortimer D, Rose M, et al. Dioxins (PCDD/Fs) and PCBs in offal:Occurrence and dietary exposure[J]. Chemosphere,2010,81(4):536-540.
    [68]Hsu J, Chen C, Liao P. Elevated PCDD/F levels and distinctive PCDD/F congener profiles in free range eggs[J]. Journal of agricultural and food chemistry,2010,58(13):7708-7714.
    [69]韩见龙.浙江省二恶英、多氯联苯污染水平及其对人体健康危害的风险评价研究[D].浙江大学,2011.
    [70]杨志军,张青,倪余文,等.牡蛎和贻贝中二噁英及多氯联苯同类物的分布[J].生态环境,2004,13(4):512-514.
    [71]刘斌,张立实,张建清,等.深圳市部分市售禽类制品二噁英污染水平研究[J].中国食品卫生杂志,2010,22(1):6-10.
    [72]Zhang J, Jiang Y, Zhou J, et al. Concentrations of PCDD/PCDFs and PCBs in retail foods and an assessment of dietary intake for local population of Shenzhen in China[J]. Environment international,2008,34(6):799-803.
    [73]Weber L W, Zesch A, Rozman K. Penetration, distribution and kinetics of 2,3,7, 8-tetrachlorodibenzo-p-dioxin in human skin in vitro[J]. Archives of toxicology,1991,65(5):421-428.
    [74]陈学敏,杨克政.现代环境卫生学[M].北京市:人民卫生出版社,2008.
    [75]金一和,陈慧池,唐慧君,等.大连和沈阳两市区79例母乳中二(口恶)英污染水平调查[J].中华预防医学杂志,2003,37(6):439-441.
    [76]王丽华.汽车铸造厂二噁英类化合物的测定分析及其与工人肿瘤痛死亡的关联研究[D].华中科技大学,2012.
    [77]沈海涛,韩见龙,任一平.农产品中二噁英类似物含量及人体摄入量的初步评估[J].环境化学,2007,26(2):269-270.
    [78]Nikolau B J, Ohlrogge J B, Wurtele E S. Plant biotin-containing carboxylases[J]. Archives of Biochemistry and Biophysics,2003,414(2):211-222.
    [79]Abu-Elheiga L, Matzuk M M, Kordari P, et al. Mutant mice lacking acetyl-CoA carboxylase 1 are embryonically lethal[J]. Proceedings of the National Academy of Sciences of the United States of America,2005,102(34):12011-12016.
    [80]Foster D W. The role of the carnitine system in human metabolism[J]. Ann N Y Acad Sci, 2004,1033:1-16.
    [81]Abu-Elheiga L, Oh W, Kordari P, et al. Acetyl-CoA carboxylase 2 mutant mice are protected against obesity and diabetes induced by high-fat/high-carbohydrate diets[J]. Proceedings of the National Academy of Sciences,2003,100(18):10207-10212.
    [82]Saha A K, Ruderman N B. Malonyl-CoA and AMP-activated protein kinase:an expanding partnership[J]. Molecular and cellular biochemistry,2003,253(1):65-70.
    [83]Berggreen C, Gormand A, Omar B, et al. Protein kinase B activity is required for the effects of insulin on lipid metabolism in adipocytes[J]. American Journal of Physiology-Endocrinology And Metabolism,2009,296(4):E635-E646.
    [84]Kusakabe T, Maeda M, Hoshi N, et al. Fatty Acid Synthase Is Expressed Mainly in Adult Hormone-sensitive Cells or Cells with High Lipid Metabolism and in Proliferating Fetal Cells 1[J]. Journal of Histochemistry & Cytochemistry,2000,48(5):613-622.
    [85]Kim T, Freake H C. High carbohydrate diet and starvation regulate lipogenic mRNA in rats in a tissue-specific manner[J]. The Journal of nutrition,1996,126(3):611-617.
    [86]Yin D, Clarke S D, Peters J L, et al. Somatotropin-dependent decrease in fatty acid synthase mRNA abundance in 3T3-F442A adipocytes is the result of a decrease in both gene transcription and mRNA stability.[J]. Biochemical Journal,1998,331(Pt 3):815.
    [87]Stapleton S R, Mitchell D A, Salati L M, et al. Triiodothyronine stimulates transcription of the fatty acid synthase gene in chick embryo hepatocytes in culture. Insulin and insulin-like growth factor amplify that effect.[J]. Journal of Biological Chemistry,1990,265(30): 18442-18446.
    [88]曾凡勇,秦锐,郭锡熔.脂肪酸合成酶在高脂饮食诱导的肥胖易感和肥胖抗性大鼠白色脂肪组织中的表达差异[J].临床儿科杂志,2007,25(1):54-57.
    [89]Miyazaki M, Kim Y, Ntambi J M. A lipogenic diet in mice with a disruption of the stearoyl-CoA desaturase 1 gene reveals a stringent requirement of endogenous monounsaturated fatty acids for triglyceride synthesis[J]. Journal of lipid research,2001,42(7):1018-1024.
    [90]Jones B H, Maher M A, Banz W J, et al. Adipose tissue stearoyl-CoA desaturase mRNA is increased by obesity and decreased by polyunsaturated fatty acids[J], American Journal of Physiology-Endocrinology And Metabolism,1996,271(1):E44-E49.
    [91]Choi Y, Park Y, Pariza M W, et al. Regulation of stearoyl-CoA desaturase activity by the trans-10,cis-12 isomer of conjugated linoleic acid in HepG2 cells[J]. Biochem Biophys Res Commun,2001,284(3):689-693.
    [92]Miller C W, Waters K M, Ntambi J M. Regulation of hepatic stearoyl-CoA desaturase gene 1 by vitamin A[J]. Biochemical and Biophysical Research Communications,1997,231(1):206-210.
    [93]Hardie D G. The AMP-activated protein kinase pathway-new players upstream and downstream[J]. Journal of cell science,2004,117(23):5479-5487.
    [94]Dobrzyn A, Ntambi J M. The role of stearoyl-CoA desaturase in body weight regulation[J]. Trends in cardiovascular medicine,2004,14(2):77-81.
    [95]Glass C K, Rosenfeld M G. The coregulator exchange in transcriptional functions of nuclear receptors[J]. Genes & development,2000,14(2):121-141.
    [96]Eberle D, Hegarty B, Bossard P, et al. SREBP transcription factors:master regulators of lipid homeostasis.[J]. Biochimie,2004,86(11):839.
    [97]Joseph S B, Laffitte B A, Patel P H, et al. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors[J]. Journal of Biological Chemistry,2002, 277(13):11019-11025.
    [98]Chu K, Miyazaki M, Man W C, et al. Stearoyl-coenzyme A desaturase 1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation[J]. Molecular and cellular biology,2006,26(18):6786-6798.
    [99]Talukdar S, Hillgartner F B. The mechanism mediating the activation of acetyl-coenzyme A carboxylase-alpha gene transcription by the liver X receptor agonist T0-901317[J]. J Lipid Res, 2006,47(11):2451-2461.
    [100]Kaplan R, Zhang T, Hernandez M, et al. Regulation of the angiopoietin-like protein 3 gene by LXR[J]. Journal of lipid research,2003,44(1):136-143.
    [101]Koishi R, Ando Y, Ono M, et al. Angptl3 regulates lipid metabolism in mice[J]. Nature genetics,2002,30(2):151-157.
    [102]Tobin K A R, Ulven S M, Schuster G U, et al. Liver X receptors as insulin-mediating factors in fatty acid and cholesterol biosynthesis[J]. Journal of Biological Chemistry,2002,277(12): 10691.
    [103]Brown M S, Goldstein J L. The SREBP Pathway:Regulation review of cholesterol metabolism by proteolysis of a membrane-bound transcription factor[J]. Cell,1997,89:331-340.
    [104]Horton J D, Goldstein J L, Brown M S. SREBPs:activators of the complete program of cholesterol and fatty acid synthesis in the liver[J]. Journal of Clinical Investigation,2002, 109(9): 1125-1132.
    [105]Mcpherson R, Gauthier A. Molecular regulation of SREBP function:the Insig-SCAP connection and isoform-specific modulation of lipid synthesis[J]. Biochemistry and cell biology, 2004,82(1):201-211.
    [106]Osborne T F. Sterol regulatory element-binding proteins (SREBPs):key regulators of nutritional homeostasis and insulin action[J]. Journal of biological chemistry,2000,275(42): 32379-32382.
    [107]Darimont C, Avanti O, Zbinden I, et al. Liver X receptor preferentially activates de novo lipogenesis in human preadipocytes[J]. Biochimie,2006,88(3):309-318.
    [108]Kakuma T, Lee Y, Higa M, et al. Leptin, troglitazone, and the expression of sterol regulatory element binding proteins in liver and pancreatic islets[J]. Proceedings of the National Academy of Sciences,2000,97(15):8536-8541.
    [109]Ruiz-Cortes Z T, Martel-Kennes Y, Gevry N Y, et al. Biphasic effects of leptin in porcine granulosa cells[J]. Biology of reproduction,2003,68(3):789-796.
    [110]Shimomura I, Bashmakov Y, Ikemoto S, et al. Insulin selectively increases SREBP-lc mRNA in the livers of rats with streptozotocin-induced diabetes[J]. Proceedings of the National Academy of Sciences,1999,96(24):13656-13661.
    [111]Wang H, Kouri G, Wollheim C B. ER stress and SREBP-1 activation are implicated in β-cell glucolipotoxicity[J]. Journal of cell science,2005,118(17):3905-3915.
    [112]Xu J, Zimmer D B. Differential regulation of A gamma and G gamma fetal hemoglobin mRNA levels by hydroxyurea and butyrate.[J]. Experimental hematology,1998,26(3):265.
    [113]艾正琳,陈东风,刘重阳,等.固醇调节元件结合蛋白-1c在大鼠非酒精性脂肪性肝炎中的表达及意义[J].重庆医学,2007,36(8):695-697.
    [114]Yamashita H, Takenoshita M, Sakurai M, et al. A glucose-responsive transcription factor that regulates carbohydrate metabolism in the liver[J]. Proceedings of the National Academy of Sciences,2001,98(16):9116-9121.
    [115]Kawaguchi T, Takenoshita M, Kabashima T, et al. Glucose and cAMP regulate the L-type pyruvate kinase gene by phosphorylation/dephosphorylation of the carbohydrate response element binding protein[J]. Proceedings of the National Academy of Sciences,2001,98(24): 13710-13715.
    [116]Stoeckman A K, Ma L, Towle H C. MIx is the functional heteromeric partner of the carbohydrate response element-binding protein in glucose regulation of lipogenic enzyme genes[J]. Journal of Biological Chemistry,2004,279(15):15662-15669.
    [117]Adamson A W, Suchankova G, Rufo C, et al. Hepatocyte nuclear factor-4a contributes to carbohydrate-induced transcriptional activation of hepatic fatty acid synthase[J]. Biochemical Journal,2006,399(Pt 2):285.
    [118]Da Silva Xavier G, Rutter G A, Diraison F, et al. ChREBP binding to fatty acid synthase and L-type pyruvate kinase genes is stimulated by glucose in pancreatic P-cells[J]. Journal of lipid research,2006,47(11):2482-2491.
    [119]Iizuka K, Bruick R K, Liang G, et al. Deficiency of carbohydrate response element-binding protein (ChREBP) reduces lipogenesis as well as glycolysis[J]. Proceedings of the National Academy of Sciences of the United States of America,2004,101(19):7281-7286.
    [120]Li M V, Chang B, Imamura M, et al. Glucose-dependent transcriptional regulation by an evolutionarily conserved glucose-sensing module[J]. Diabetes,2006,55(5):1179-1189.
    [121]Dentin R, Benhamed F, Pegorier J, et al. Polyunsaturated fatty acids suppress glycolytic and lipogenic genes through the inhibition of ChREBP nuclear protein translocation[J]. Journal of Clinical Investigation,2005,115(10):2843.
    [122]Dentin R, Benhamed F, Hainault I, et al. Liver-specific inhibition of ChREBP improves hepatic steatosis and insulin resistance in ob/ob mice[J]. Diabetes,2006,55(8):2159-2170.
    [123]Adser H, Wojtaszewski J, Jakobsen A H, et al. Interleukin-6 modifies mRNA expression in mouse skeletal muscle[J]. Acta Physiologica,2011,202(2):165-173.
    [124]Wang L, Mascher H, Psilander N, et al. Resistance exercise enhances the molecular signaling of mitochondrial biogenesis induced by endurance exercise in human skeletal muscle[J]. Journal of applied physiology,2011,111(5):1335-1344.
    [125]Van Proeyen K, De Bock K, Hespel P. Training in the fasted state facilitates re-activation of eEF2 activity during recovery from endurance exercise[J]. European journal of applied physiology,2011,111(7):1297-1305.
    [126]Sriwijitkamol A, Ivy J L, Christ-Roberts C, et al. LKB1-AMPK signaling in muscle from obese insulin-resistant Zucker rats and effects of training[J]. American Journal of Physiology-Endocrinology And Metabolism,2006,290(5):E925-E932.
    [127]Dobrzyn P, Pyrkowska A, Jazurek M, et al. Endurance training-induced accumulation of muscle triglycerides is coupled to upregulation of stearoyl-CoA desaturase 1[J]. Journal of Applied Physiology,2010,109(6):1653-1661.
    [128]Morifuji M, Sakai K, Sanbongi C, et al. Dietary whey protein downregulates fatty acid synthesis in the liver, but upregulates it in skeletal muscle of exercise-trained rats[J]. Nutrition, 2005,21(10):1052-1058.
    [129]Rector R S, Thyfault J P, Morris R T, et al. Daily exercise increases hepatic fatty acid oxidation and prevents steatosis in Otsuka Long-Evans Tokushima Fatty rats[J]. American Journal of Physiology-Gastrointestinal and Liver Physiology,2008,294(3):G619-G626.
    [130]Griffiths M A, Baker D H, Yu X, et al. Effects of acute exercise on hepatic lipogenic enzymes in fasted and refed rats[J]. Journal of Applied Physiology,1995,79(3):879-885.
    [131]Faulconnier Y, Arnal M, Patureau Mirand P, et al. Isomers of conjugated linoleic acid decrease plasma lipids and stimulate adipose tissue lipogenesis without changing adipose weight in post-prandial adult sedentary or trained Wistar rat[J]. The Journal of Nutritional Biochemistry, 2004,15(12):741-748.
    [132]Petridou A, Tsalouhidou S, Tsalis G, et al. Long-term exercise increases the DNA binding activity of peroxisome proliferator-activated receptor gamma in rat adipose tissue[J]. Metabolism, 2007,56(8):1029-1036.
    [133]Summermatter S, Baum O, Santos G, et al. Peroxisome proliferator-activated receptor y coactivator la (PGC-la) promotes skeletal muscle lipid refueling in vivo by activating de novo lipogenesis and the pentose phosphate pathway[J]. Journal of Biological Chemistry,2010, 285(43):32793-32800.
    [134]Aoi W, Naito Y, Hang L P, et al. Regular exercise prevents high-sucrose diet-induced fatty liver via improvement of hepatic lipid metabolism[J]. Biochemical and biophysical research communications,2011,413(2):330-335.
    [135]唐量,田振军,熊正英,等.应用基因芯片技术对疲劳性运动小鼠脑组织脂肪酸代谢相关基因表达的初步研究[J].中国应用生理学杂志,2005,21(2):137-139.
    [136]Dube J J, Amati F, Toledo F G, et al. Effects of weight loss and exercise on insulin resistance, and intramyocellular triacylglycerol, diacylglycerol and ceramide[J]. Diabetologia, 2011,54(5):1147-1156.
    [137]Yasari S, Prud Homme D, Wang D, et al. Exercise training decreases hepatic SCD-1 gene expression and protein content in rats[J]. Molecular and cellular biochemistry,2010,335(1): 291-299.
    [138]Ikeda S, Miyazaki H, Nakatani T, et al. Up-regulation of SREBP-lc and lipogenic genes in skeletal muscles after exercise training[Z].2002:296,395-400.
    [139]Pighon A, Gutkowska J, Jankowski M, et al. Exercise training in ovariectomized rats stimulates estrogenic-like effects on expression of genes involved in lipid accumulation and subclinical inflammation in liver[J]. Metabolism,2011,60(5):629-639.
    [140]Rocco D D, Okuda L S, Pinto R S, et al. Aerobic exercise improves reverse cholesterol transport in cholesteryl ester transfer protein transgenic mice[J]. Lipids,2011,46(7):617-625.
    [141]Kazeminasab M M, Ghaedi K, Esfarjani F, et al. Endurance training enhances LXR expression in the liver of male Wistar rats[J]. Research in Pharmaceutical Sciences,2012,7(5): S544.
    [142]Nadeau K J, Ehlers L B, Aguirre L E, et al. Exercise training and calorie restriction increase SREBP-1 expression and intramuscular triglyceride in skeletal muscle[J]. American Journal of Physiology-Endocrinology And Metabolism,2006,291(1):E90-E98.
    [143]Schenk S, Horowitz J F. Acute exercise increases triglyceride synthesis in skeletal muscle and prevents fatty acid-induced insulin resistance[J]. Journal of Clinical Investigation,2007, 117(6):1690.
    [144]Cintra D E, Ropelle E R, Vitto M F, et al. Reversion of hepatic steatosis by exercise training in obese mice:The role of sterol regulatory element-binding protein-lc[J]. Life Sciences,2012.
    [145]刘建红,黄森,林文弢,等.有氧运动对高糖高脂膳食大鼠肝脏碳水化合物反应元件结合蛋白mRNA表达的影响[J].中国运动医学杂志,2008,27(5):624-626.
    [146]Frueh F W, Hayashibara K C, Brown P O, et al. Use of cDNA microarrays to analyze dioxin-induced changes in human liver gene expression[J]. Toxicology letters,2001,122(3): 189-203.
    [147]Bertazzi P A, Consonni D, Bachetti S, et al. Health effects of dioxin exposure:a 20-year mortality study[J]. American Journal of Epidemiology,2001,153(11):1031-1044.
    [148]Sato S, Shirakawa H, Tomita S, et al. Low-dose dioxins alter gene expression related to cholesterol biosynthesis, lipogenesis, and glucose metabolism through the aryl hydrocarbon receptor-mediated pathway in mouse liver[J]. Toxicology and applied pharmacology,2008,229(1): 10-19.
    [149]Forgacs A L, Kent M N, Makley M K, et al. Comparative metabolomic and genomic analyses of TCDD-elicited metabolic disruption in mouse and rat liver[J]. Toxicological Sciences, 2012,125(1):41-55.
    [150]Angrish M M, Dominici C Y, Zacharewski T R. TCDD-Elicited Effects on Liver, Serum, and Adipose Lipid Composition in C57BL/6 Mice[J]. Toxicological Sciences,2012.
    [151]Mckim J M, Marien K, Schaup H W, et al. Alterations of hepatic acetyl-CoA carboxylase by 2,3,7,8-tetrachlorodibenzo-p-dioxin[J]. Lipids,1991,26(7):521-525.
    [152]Nishiumi S, Yoshida M, Azuma T, et al.2,3,7,8-tetrachlorodibenzo-p-dioxin impairs an insulin signaling pathway through the induction of tumor necrosis factor-alpha in adipocytes[J]. Toxicol Sci,2010,115(2):482-491.
    [153]Angrish M M, Jones A D, Harkema J R, et al. Aryl Hydrocarbon Receptor-Mediated Induction of Stearoyl-CoA Desaturase 1 Alters Hepatic Fatty Acid Composition in TCDD-Elicited Steatosis[J]. Toxicological Sciences,2011,124(2):299-310.
    [154]Lee C, Yao Y, Chen H, et al. Fatty liver and hepatic function for residents with markedly high serum PCDD/Fs levels in Taiwan[J]. Journal of Toxicology and Environmental Health, Part A,2006,69(5):367-380.
    [155]Remillard R B, Bunce N J. Linking dioxins to diabetes:epidemiology and biologic plausibility.[J]. Environmental health perspectives,2002,110(9):853.
    [156]Olsen H, Enan E, Matsumura F. Regulation of glucose transport in the NIH 3T3 L1 preadipocyte cell line by TCDD.[J]. Environmental health perspectives,1994,102(5):454.
    [157]Nishiumi S, Yabushita Y, Furuyashiki T, et al. Involvement of SREBPs in 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced disruption of lipid metabolism in male guinea pig[J]. Toxicol Appl Pharmacol,2008,229(3):281-289.
    [158]Croutch C R, Lebofsky M, Schramm K, et al.2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD) and 1,2,3,4,7,8-hexachlorodibenzo-p-dioxin (HxCDD) alter body weight by decreasing insulin-like growth factor I (IGF-I) signaling[J]. Toxicological Sciences,2005,85(1): 560-571.
    [159]严翊,谢敏豪.大鼠游泳运动的最大乳酸稳态负荷的确定一乳酸最小试验[J].北京体育大学学报,2010(9):43-45.
    [160]吴景欢.亚慢性接触TCDD对成年大鼠空间学习和记忆及海马CA1区长时程增强的影响[D].汕头大学,2010.
    [161]Ciftci O, Tanyildizi S, Godekmerdan A. Protective effect of curcumin on immune system and body weight gain on rats intoxicated with 2,3,7,8-Tetrachlorodibenzo-p-dioxin (TCDD)[J]. Immunopharmacology and Immunotoxicology,2010,32(1):99-104.
    [162]Boverhof D R, Burgoon L D, Tashiro C, et al. Temporal and dose-dependent hepatic gene expression patterns in mice provide new insights into TCDD-mediated hepatotoxicity[J]. Toxicological Sciences,2005,85(2):1048-1063.
    [163]Tuomisto J T, Pohjanvirta R, Unkila M, et al. TCDD-induced anorexia and wasting syndrome in rats:effects of diet-induced obesity and nutrition[J]. Pharmacology Biochemistry and Behavior,1999,62(4):735-742.
    [164]史仍飞,袁海平,刘学,等.不同强度运动对大鼠脂质代谢的影响及机理探讨[J].中国运动医学杂志,2004,22(5):509-510.
    [165]吴小平,张胜.不同强度耐力运动对血清总胆固醇,脂蛋白水平的影响[J].体育科技,1996.
    [166]颜宜苣,张勇.有氧运动对高胆固醇血症大鼠肝脏低密度脂蛋白受体活性调节…[J].中国应用生理学杂志,1997,13(1):18-20.
    [167]赵斐,张娜,张勇.有氧运动改善高脂血症分子机理的研究IV.有氧运动上调饮食性高脂血症大鼠肝脏LDL-R基因表达[J].中国运动医学杂志,2002(2).
    [168]蔡蕾,陈吉棣.运动和山楂对大鼠高脂血症的治疗作用及其机理的研究[J].中国运动医学杂志,2000,19(1):29-32.
    [169]Peet D J, Turley S D, Ma W, et al. Cholesterol and bile acid metabolism are impaired in mice lacking the nuclear oxysterol receptor LXRa[J]. Cell,1998,93(5):693-704.
    [170]Schultz J R, Tu H, Luk A, et al. Role of LXRs in control of lipogenesis[J]. Genes & Development,2000,14(22):2831-2838.
    [171]Yang T, Espenshade P J, Wright M E, et al. Crucial Step in Cholesterol Homeostasis-Sterols Promote Binding of SCAP to INSIG-1, a Membrane Protein that Facilitates Retention of SREBPs in ER[J]. Cell,2002,110(4):489-500.
    [172]Dentin R, Pegorier J, Benhamed F, et al. Hepatic glucokinase is required for the synergistic action of ChREBP and SREBP-lc on glycolytic and lipogenic gene expression[J]. Journal of Biological Chemistry,2004,279(19):20314-20326.
    [173]Strable M S, Ntambi J M. Genetic control of de novo lipogenesis:role in diet-induced obesity[J]. Critical reviews in biochemistry and molecular biology,2010,45(3):199-214.
    [174]Munday M. Regulation of mammalian acetyl-CoA carboxylase[J]. Biochemical Society Transactions,2002,30:1059-1064.
    [175]Lee-Young R S, Koufogiannis G, Canny B J, et al. Acute exercise does not cause sustained elevations in AMPK signaling or expression.[J]. Medicine and science in sports and exercise, 2008,40(8):1490.
    [176]Rector R S, Thyfault J P, Laye M J, et al. Cessation of daily exercise dramatically alters precursors of hepatic steatosis in Otsuka Long-Evans Tokushima Fatty (OLETF) rats[J]. The Journal of physiology,2008,586(17):4241-4249.
    [177]Menendez J A, Colomer R, Lupu R. Why does tumor-associated fatty acid synthase (oncogenic antigen-519) ignore dietary fatty acids?[J]. Medical hypotheses,2005,64(2):342.

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