维生素E对二(口恶)英染毒小鼠肝脏细胞色素P450酶基因转录的影响
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国家自然科学基金


Effect of Vitamin E on Transcription Activity of Liver CYP450 Gene in Mice Treated with TCDD
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    摘要:

    目的研究维生素E对2,3,7,8-四氯代二苯并二噁英(TCDD)染毒小鼠肝脏细胞色素P450酶1A1、1A2、1B1基因转录的影响。方法设计了5个实验组,将45只小鼠随机分为5组,5组动物给予TCDD和维生素E的水平依次为:TCDD0 ng/kg和VE0 mg/kg、TCDD100 ng/kg和VE0 mg/kg、TCDD100 ng/kg和VE20 mg/kg、TCDD100 ng/kg和VE100 mg/kg、TCDD100 ng/kg和VE500 mg/kg。喂食4周后取其肝脏,用real-time PCR法测小鼠细胞色素P450酶1A1、1A2、1B1基因mRNA水平。结果TCDD染毒小鼠肝脏细胞色素P450酶1A1、1A2 mRNA水平与对照组相比有升高的趋势,而细胞色素P450酶1B1 mRNA水平明显降低。染毒并给予维生素E20 mg/kg组,其肝脏CYP4501A1的mRNA水平有降低趋势,随着维生素E剂量的增加,YP450 1A1的mRNA水平反而有升高的趋势,当维生素E剂量为500 mg/kg时,其肝脏CYP450 1A1的mRNA明显高于TCDD染毒组。CYP450 1A2的mRNA水平随着维生素E剂量的增加有降低的趋势,在TCDD染毒并给予维生素E500 mg/kg组,其肝脏CYP450 1A2的mRNA水平明显低于TCDD染毒组。而肝脏CYP450 1B1的mRNA水平在染毒并给与维生素E500 mg/kg组,与染毒组相比有上调趋势。结论TCDD能影响或部分影响小鼠细胞色素P450酶1A1、1A2、1B1的基因转录,而维生素E能在一定程度上缓解TCDD的作用。

    Abstract:

    Objective To investigate the effect of vitamin E on transcription activity of liver CYP450 1A1,CYP450 1A2,CYP450 1B1 genes in mice treated with 2,3,7,8-tetrachlorodibenzo-p-dioxin(TCDD).Methods Forty-five mice were divided into 5 groups,and the levels of TCDD and vitamin E were given at a dose of 0 and 0,100 and 0,100 and 20,100 and 100,and 100 ng/kg/d and 500 mg/kg/d,respectively.After 4 weeks,livers were taken to analyze the transcription activity of CYP450 1A1,CYP450 1A2 and CYP450 1B1 genes by real-time PCR method.Reaults There was an increasing tendency of liver CYP450 1A1,CYP450 1A2 mRNA levels in the mice treated with TCDD compared with those in the control group,while CYP450 1B1 mRNA level was significantly lower than that of the control group.When vitamin E was supplemented at a dose of 20 mg/kg,there was a decreasing tendency of CYP450 1A1 mRNA levels in comparison with the group treated with TCDD.The CYP450 1A1 mRNA levels increased with the increase of vitamin E dosage,and significantly increased at vitamin E 500 mg/kg compared with those in the group treated with TCDD.The CYP450 1A2 mRNA level was decreased with increase of vitamin E dosage,and was significantly lower at vitamin E 500 mg/kg than that of the group treated with TCDD.When vitamin E was supplemented in a dose of 500 mg/kg,there was an increasing tendency of CYP450 1B1 mRNA level compared to that in the group treated with TCDD. Conclusion These results suggested that TCDD can affect or partly affect transcription activity of liver CYP450 1A1,CYP450 1A2 and CYP450 1B1 genes in mice,and vitamin E can alleviate the effect of TCDD to a certain extent.

    Key words:TCDD
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尹海萍,徐建平,周显青,王迎.维生素E对二(口恶)英染毒小鼠肝脏细胞色素P450酶基因转录的影响[J].中国比较医学杂志,2007,(12):683~687,692,771.

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  • 收稿日期:2007-07-23
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