摘要:
研究运动对2,3,7,8-四氯二苯并二噁英(2,3,7,8-TCDD)持续染毒大鼠肝脏脂质合成代谢关键酶乙酰辅酶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及转录因子肝X受体a(LXRa)蛋白表达的影响，探讨环境污染物引发代谢性疾病的发病机制，为运动锻炼防控环境健康风险提供理论支持。将24只8周龄雄性大鼠随机分为对照组(C组)、染毒组(T组)、运动染毒组(ET组)。T、ET组腹腔注射首剂量6.4 μg·kg-1(以单位体重计)的2,3,7,8-TCDD，之后每隔1周给予上述剂量的21%持续染毒，连续7周。ET组尾部负重(5%体重)进行游泳运动，每周5 d，每次30 min。8周后处死动物，计算肝脏相对重量，检测肝脏甘油三酯(TG)含量，实时荧光定量PCR检测肝脏ACC1、FAS、SCD1 mRNA表达，免疫印迹法(Western Blot)检测肝脏LXRa蛋白表达。结果显示8周2,3,7,8-TCDD持续染毒可显著增加肝脏脂质合成代谢关键酶ACC1、FAS、SCD1 mRNA及转录因子LXRa蛋白表达，8周游泳运动可显著降低染毒大鼠ACC1、FAS、SCD1 mRNA及LXRa蛋白表达。上述结果表明2,3,7,8-TCDD可以引起大鼠肝脏LXRa蛋白表达增高，进而LXRa通过调控靶基因ACC1、FAS、SCD1 mRNA的表达，造成脂质代谢紊乱，肝脏甘油三酯沉积，而有氧运动降低了肝脏中脂质的沉积，提示运动干预可以改善二噁英类污染物造成的肝脏脂质代谢紊乱。
Abstract:
To investigate the mechanisms of metabolic diseases induced by environmental pollutants, this study evaluated the effects of exercise on the expression of ACC1, FAS, SCD1 mRNA, which are crucial enzymes during lipid metabolism in the liver, and the transcriptional factor LXRa in continuously 2,3,7,8-TCDD exposed rats, and consequently, provided the theoretic support for controlling and decreasing the environmental risks by exercise. Twenty-four 8-week old male SD rats were randomly assigned into control (C) group, toxic (T) group and exercise toxic (ET) group. The rats in the latter two groups were injected intraperitoneally with 2,3,7,8-TCDD (dissolved in the corn oil) at a dose of 6.4 μg·kg-1 of body weight during the first week. Thereafter, a maintenance dose of 21% of first dose were administered every week during the following 2-8 weeks. In addition, the rats in ET group swam 5 times per week (at least 30 min every time) for eight weeks with a load of 5% body weight attached to the tails. After finishing the experiment, the livers from the rats of all three groups were weighted and collected for the following measures, including the triglyceride (TG), the expression of ACC1, FAS, and SCD1 mRNA determined by RT-PCR, and the concentration of LXRa determined via Western Blot. Continuous exposure to 2,3,7,8-TCDD increased the mRNA expression of the crucial enzymes during liver lipid metabolism and the concentration of TG and the transcriptional factor LXRa, while these indexes might be decreased by 8 weeks of swimming. The exposure of 2,3,7,8-TCDD could increase the concentration of LXRa in rat liver, and then the expression of LXRa-targeted genes, including ACC1, FAS and SCD1 mRNA, might be upregulated, consequently leading to disorder of lipid metabolism and deposition of triglyceride in the liver. The results of decreasing in lipid deposition in the liver by aerobic exercise indicated that exercise could reverse the lipid metabolic disorder induced by exposure to 2,3,7,8-TCDD.
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