长期规律运动对二英染毒大鼠肝脏脂类合成相关酶基因表达的影响
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摘要
目的探讨不同周期运动对二英染毒大鼠肝脏脂肪合成相关酶基因表达的影响。方法将48只健康成年SPF级SD大鼠随机分为3组,分别为对照(玉米油)组、二英染毒组和运动干预组,每组16只。二英染毒组、运动干预组大鼠于第1周周日早晨以6.4μg/kg剂量腹腔注射染毒二英,后续每周日早晨以1.344μg/kg继续染毒;运动干预组大鼠于每周一至周五进行尾部负重游泳运动1次,每次30 min,连续实验8周。分别于实验第4、8周时,检测大鼠肝脏中甘油三酯的水平及乙酰辅酶A羧化酶1(ACC1)、脂肪酸合成酶(FAS)、硬脂酰辅酶A去饱和酶1(SCD1)mRNA的表达水平。结果在实验第4、8周时,与对照组相比,二英染毒组大鼠肝脏甘油三酯的水平较高,差异均有统计学意义(P<0.05,P<0.01)。仅在实验第8周时,与二英染毒组相比,运动干预组大鼠肝脏甘油三酯的水平较低,差异有统计学意义(P<0.01)。在实验第4周时,与对照组相比,二英染毒组大鼠肝组织ACC1、FAS mRNA的表达水平均较高,差异有统计学意义(P<0.05);而运动干预组大鼠肝组织ACC1、FAS、SCD1 mRNA的表达水平均无明显改变。在实验第8周时,大鼠肝组织ACC1、FAS、SCD1 mRNA的表达水平依次为二英染毒组>运动干预组>对照组,差异均有统计学意义(P<0.05或P<0.01);在实验第8周时,二英染毒组和运动干预组大鼠肝组织ACC1、FAS、SCD1 mRNA的表达水平均高于实验第4周,差异有统计学意义(P<0.01或P<0.05)。结论二英染毒可使大鼠肝脏中ACC1、FAS、SCD1 mRNA表达水平上升,促进肝脏脂质合成代谢,出现肝脏脂质沉积。长时间规律运动可以降低肝脏甘油三酯的水平及下调ACC1、FAS、SCD1mRNA表达水平,改善二英污染物造成的肝脏脂质沉积。
Objective To investigate the effects of different exercise durations on the expression of fat synthesis-related enzymes in the liver of rats exposed to dioxin. Methods A total of 48 SPF SD rats were randomly divided into three groups(sixteen in each group),control group,exposure group and exercise group. The rats in exposure group and exercise group were treated with dioxin at the dose of 6.4 μg/kg body weight through intraperitoneal injection on Sunday morning in the first week and followed by 1.344 μg/kg body weight every Sunday morning for eight consecutive weeks, and the exercise group performed30 min-swimming with a load once a day from Monday to Friday. At the 4 th and 8 th week of the experiment,the levels of triglycerides and acetyl-CoA carboxylase 1(ACC1),fatty acid synthase(FAS),stearyl-CoA desaturase 1(SCD1) mRNA expression in liver were detetermined respectively. Results Compared with the control group,triglyceride content in liver of exposure group was higher(P<0.05 or P<0.01) at week 4 and 8 liver of the experiment. Compared with the exposure group,triglyceride content in liver of exercise group was lower(P<0.01) at week 8. At week 4, ACC1 and FAS mRNA expression in liver of exposure group were higher than those in the control group(P<0.05), and ACC1, FAS, SCD1 mRNA expression in liver of exercise group had no obvious change. At week 8, in liver tissue ACC1, FAS, SCD1 m RNA expression levels in the exposure group were higher than those in the exercise group, the exercise group were higher than the control group(P<0.05 or P<0.01).ACC1,FAS and SCD1 mRNA expression in liver of the exposure group and the exercise group at week 8 were higher than those at week 4(P<0.01 or P<0.05). Conclusion Dioxin exposure may increase triglyceride content of rat liver and may promote lipid synthesis metabolism causing lipid deposition in liver through increasing ACC1,FAS and SCD1 mRNA expression.Regular exercise for a long time may reduce triglyceride content in the liver and improve lipid deposition caused by dioxin exposure through down-regulating ACC1,FAS and SCD1 mRNA expression.
Objective To investigate the effects of different exercise durations on the expression of fat synthesis-related enzymes in the liver of rats exposed to dioxin. Methods A total of 48 SPF SD rats were randomly divided into three groups(sixteen in each group),control group,exposure group and exercise group. The rats in exposure group and exercise group were treated with dioxin at the dose of 6.4 μg/kg body weight through intraperitoneal injection on Sunday morning in the first week and followed by 1.344 μg/kg body weight every Sunday morning for eight consecutive weeks, and the exercise group performed30 min-swimming with a load once a day from Monday to Friday. At the 4 th and 8 th week of the experiment,the levels of triglycerides and acetyl-CoA carboxylase 1(ACC1),fatty acid synthase(FAS),stearyl-CoA desaturase 1(SCD1) mRNA expression in liver were detetermined respectively. Results Compared with the control group,triglyceride content in liver of exposure group was higher(P<0.05 or P<0.01) at week 4 and 8 liver of the experiment. Compared with the exposure group,triglyceride content in liver of exercise group was lower(P<0.01) at week 8. At week 4, ACC1 and FAS mRNA expression in liver of exposure group were higher than those in the control group(P<0.05), and ACC1, FAS, SCD1 mRNA expression in liver of exercise group had no obvious change. At week 8, in liver tissue ACC1, FAS, SCD1 m RNA expression levels in the exposure group were higher than those in the exercise group, the exercise group were higher than the control group(P<0.05 or P<0.01).ACC1,FAS and SCD1 mRNA expression in liver of the exposure group and the exercise group at week 8 were higher than those at week 4(P<0.01 or P<0.05). Conclusion Dioxin exposure may increase triglyceride content of rat liver and may promote lipid synthesis metabolism causing lipid deposition in liver through increasing ACC1,FAS and SCD1 mRNA expression.Regular exercise for a long time may reduce triglyceride content in the liver and improve lipid deposition caused by dioxin exposure through down-regulating ACC1,FAS and SCD1 mRNA expression.
引文
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[17]Aoi W,Naito Y,Hang LP,et al. Regular exercise prevents highsucrose diet-induced fatty liver via improvement of hepatic lipidmetabolism[J]. Biochem Biophys Res Commun,2011,413:330-335.
[18]Yasari S,Prud HD,Wang D,et al. Exercise training decreases hepatic SCD-1 gene expression and protein content in rats[J]. Mol Cell Biochem,2010,335:291-299.
[2]Boyd SA,Sallach JB,Zhang Y,et al. Sequestration of TCDD by activated carbon eliminates bioavailability and the suppression of immune function in mice[J]. Environ Toxicol Chem,2017,36:2671-2678.
[3]Yon C,Weiner JA,Chun DS,et al. Mechanistic insight into the effects of aryl hydrocarbon receptor activation on osteogenic differentiation[J]. Bone Rep,2017,16:51-59.
[4]Sofo V,Gotte M,Lagana AS,et al. Correlation between dioxin and endometriosis:anepigenetic route to unravel the pathogenesis of the disease[J]. Arch Gynecol Obstet, 2015,292:973-986.
[5]Chevrier J, Warner M, Gunier RB, et al. Serum dioxin concentrations and thyroid hormone levels in the seveso women's health study[J].Am J Epidemiol, 2014,180:490-498.
[6]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]. Int Archives Occup Environ Health,2002,75:60-66.
[7]焦守海.2,3,7,8-四氯苯并二噁英(TCDD)对高脂喂养大鼠糖代谢和脂代谢影响研究[D].济南:济南大学,2011.
[8]蔡爱芳,陆一帆.2,3,7,8-四氯二苯并二噁英染毒对大鼠肝脏脂肪合成相关酶基因达的影响[J].环境与健康杂志,2017,34(9):778-781.
[9]杨静宜,徐俊华.运动处方[M].北京:高等教育出版社,2009:114-125.
[10]Croutch CR,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]. Toxicol Sci, 2005,85:560-571.
[11]Bindesb ll C,Tan S,Bott D,et al. TCDD-inducible poly-ADPribose polymerase(TIPARP/PARP7)mono-ADP-ribosylates and coactivates liver X receptors[J]. Biochem J, 2016,473:899-910.
[12]Joseph SB,Laffitte BA, Patel PH,et al. Direct and indirect mechanisms for regulation of fatty acid synthase gene expression by liver X receptors[J]. J Biol Chem, 2002,277:11019-11025.
[13]Chu K,Miyazaki M,Man WC,et al. Stearoyl-coenzyme A desaturase1 deficiency protects against hypertriglyceridemia and increases plasma high-density lipoprotein cholesterol induced by liver X receptor activation[J]. Mol Cell Biol, 2006, 26:6786-6798.
[14]Talukdar S, Hillgartner FB. The mechanism mediating the activation of acetyl-coenzyme A carboxylase-alpha gene transcription by the liver X receptor agonist TO-901317[J]. J Lipid Res,2006,47:2451-2461.
[15]Lee-Young RS, Koufogiannis G, Canny BJ, et al. Acute exercise does not cause sustained elevations in AMPK signaling or expression.[J].Med Sci Sports Exere, 2008,40:1490-1494.
[16]Rector RS,Thyfault JP,Laye MJ,et al. Cessation of daily exercise dramatically alters precursors of hepatic steatosis in Otsuka LongEvans Tokushima Fatty(OLETF)rats[J]. J Physiol,2008,586:4241-4249.
[17]Aoi W,Naito Y,Hang LP,et al. Regular exercise prevents highsucrose diet-induced fatty liver via improvement of hepatic lipidmetabolism[J]. Biochem Biophys Res Commun,2011,413:330-335.
[18]Yasari S,Prud HD,Wang D,et al. Exercise training decreases hepatic SCD-1 gene expression and protein content in rats[J]. Mol Cell Biochem,2010,335:291-299.