2,3,7,8-四氯二苯并二英对大鼠肝脏脂肪合成相关酶基因表达的影响
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摘要
目的研究2,3,7,8-四氯二苯并二英(2,3,7,8-TCDD)引起大鼠肝脏发生脂肪变性的作用机制。方法将16只健康成年SPF级雄性SD大鼠随机分为2组,分别为(玉米油)对照组和2,3,7,8-TCDD染毒组,每组8只。首次以6.4μg/kg剂量进行腹腔注射染毒,后每隔1周以首次剂量的21%(1.344μg/kg)进行染毒,染毒容量为10 ml/kg,连续3周。于首次染毒后4周末,测定血清和肝脏中甘油三酯含量,采用RT-PCR法检测肝脏脂肪合成相关酶乙酰辅酶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)m RNA的表达水平。结果与对照组比较,2,3,7,8-TCDD染毒组大鼠肝脏中的甘油三酯含量较高,差异有统计学意义(P<0.05);而血清中的甘油三酯含量无明显改变。与对照组比较,2,3,7,8-TCDD染毒组大鼠肝组织中ACC1、FAS m RNA的表达水平均较高,差异有统计学意义(P<0.05);而SCD1 m RNA的表达水平无明显改变。结论 2,3,7,8-TCDD可通过上调肝组织ACC1、FAS m RNA的表达水平,来干扰肝脏脂质合成代谢,造成肝脏脂质沉积。
Objective To investigate the mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced steatosis in rat liver.Methods A total of 16 health SPF level SD rats were randomly divided into two groups(eight in each group), namely the control and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure groups. The first dose of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin was 6.4 μg/kg body weight, thereafter, a maintenance dosage by 21% of the first dose(1.344 μg/kg) weekly for three weeks, and treatments were conducted with capacity of 10 ml/kg body weight by intraperitoneal injection. Four weeks after the first expourse,triglyceride levels in serum and liver were detected, and acetyl-Co A carboxylase(ACC1), fatty acid synthetase(FAS), stearoylCo A desaturase1(SCD1) genes relative expression levels in liver were detected by using real time-PCR. Results Compared with the control group, triglyceride in liver was higher in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure group(P<0.05). There was no significant difference in serum triglyceride between control group and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure group. Compared with the control group, ACC1 and FAS m RNA expression level were higher in 2, 3, 7, 8-tetrachlorodibenzop-dioxin exposure group(P<0.05). There was no significant difference in SCD1 m RNA expression level between control group and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure group. Conclusion 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure may cause lipid deposition and interfere lipid synthesis in liver through up-regulating ACC1 and FAS m RNA expression levels.
Objective To investigate the mechanism of 2,3,7,8-tetrachlorodibenzo-p-dioxin-induced steatosis in rat liver.Methods A total of 16 health SPF level SD rats were randomly divided into two groups(eight in each group), namely the control and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure groups. The first dose of 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin was 6.4 μg/kg body weight, thereafter, a maintenance dosage by 21% of the first dose(1.344 μg/kg) weekly for three weeks, and treatments were conducted with capacity of 10 ml/kg body weight by intraperitoneal injection. Four weeks after the first expourse,triglyceride levels in serum and liver were detected, and acetyl-Co A carboxylase(ACC1), fatty acid synthetase(FAS), stearoylCo A desaturase1(SCD1) genes relative expression levels in liver were detected by using real time-PCR. Results Compared with the control group, triglyceride in liver was higher in 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure group(P<0.05). There was no significant difference in serum triglyceride between control group and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure group. Compared with the control group, ACC1 and FAS m RNA expression level were higher in 2, 3, 7, 8-tetrachlorodibenzop-dioxin exposure group(P<0.05). There was no significant difference in SCD1 m RNA expression level between control group and 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure group. Conclusion 2, 3, 7, 8-tetrachlorodibenzo-p-dioxin exposure may cause lipid deposition and interfere lipid synthesis in liver through up-regulating ACC1 and FAS m RNA expression levels.
引文
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[13]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:济南大学,2011.
[2]Iszatt N,Stigum H,Govarts E,et al.Perinatal exposure to dioxins and dioxin-like compounds and infant growth and body mass index at seven years:a pooled analysis of three European birth cohorts[J].Environ Int,2016,94:399-407.
[3]Ngwa EN,Kengne AP,Tiedeu-Atogho B,et al.Persistent organic pollutants as risk factors for type 2 diabetes[J].Diabetol Metab Syndr,2015,7:41.
[4]Boffetta P,Mundt KA,Adami HO,et al.TCDD and cancer:a critical review of epidemiologic studies[J].Crit Rev Toxicol,2011,41:622-636.
[5]Wajda A,覵apczuk J,Grabowska M,et al.Cell and region specificity of aryl hydrocarbon receptor(Ah R)system in the testis and the epididymis[J].Reprod Toxicol,2017,69:286-296.
[6]PelclováD,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 Arch Occupat Environ Health,2002,75:60-66.
[7]Olsen H,Enan E,Matsumura F.Regulation of glucose transport in the NIH 3T3 LI preadipocyte cell line by TCDD[J].Environ Health Perspect,1994,102:454.
[8]Forgacs AL,Kent MN,Makley MK,et al.Comparative metabolomic and genomic analyses of TCDD-elicited metabolic disruption in mouse and rat liver[J].Toxicol Sci,2012,125:41-55.
[9]Strable MS,Ntambi JM.Genetic control of de novo lipogenesis:role in diet-induced obesity[J].Crit Rev Biochem Mole Bio,2010,45:199-214.
[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(Hx CDD)alter body weight by decreasing insulin-like growth factor I(IGF-I)signaling[J].Toxicol Sci,2005,85:560-571.
[11]Yang T,Espenshade PJ,Wright ME,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,2002,110:489-500.
[12]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,2008,229:281-289.
[13]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:济南大学,2011.