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普通猪中细胞色素P450的组成型表达与活性

Constitutive expression and activity of cytochrome P450 in conventional pigs.

作者信息

Nielsen Søren Drud, Bauhaus Yvonne, Zamaratskaia Galia, Junqueira Matheus Antunes, Blaabjerg Karoline, Petrat-Melin Bjørn, Young Jette Feveile, Rasmussen Martin Krøyer

机构信息

Department of Food Science, Aarhus University, Denmark.

Department of Food Science, BioCenter, Swedish University of Agricultural Science, Uppsala, Sweden.

出版信息

Res Vet Sci. 2017 Apr;111:75-80. doi: 10.1016/j.rvsc.2016.12.003. Epub 2016 Dec 23.

Abstract

Pigs have often been suggested to be a useful model for humans, when investigating CYP dependent events, like drug metabolism. However, comprehensive knowledge about the constitutive expression of the major CYP and corresponding transcription factors is limited. We compared the constitutive mRNA expression of aryl hydrocarbon receptor, constitutive androstane receptor and pregnane X receptor and CYP1A1, CYP1A2, CYP2A, CYP2E1 and CYP3A in liver, adipose tissue, muscle and small intestine in pigs, as well as the expression along the length of the small intestine and colon. Tissue samples were taken from female pigs, and analyzed for gene expression, as well as CYP dependent activity using qPCR and specific probe substrates, respectively. For all investigated transcription factors and CYPs the mRNA expression and activity was highest in the liver. CYP1A1 and CYP3A mRNA expression and activity was shown in all investigated tissues. Along the small intestine and colon the mRNA expression and activity of CYP1A1 and CYP3A was gradually decreased. The results demonstrated, similarity to that reported for humans, and hence adds to the use of pigs as a model for humans.

摘要

在研究细胞色素P450(CYP)依赖性事件(如药物代谢)时,猪常被认为是人类的有用模型。然而,关于主要CYP及其相应转录因子组成型表达的全面知识有限。我们比较了猪肝脏、脂肪组织、肌肉和小肠中芳烃受体、组成型雄烷受体和孕烷X受体以及CYP1A1、CYP1A2、CYP2A、CYP2E1和CYP3A的组成型mRNA表达,以及小肠和结肠全长的表达情况。从雌性猪采集组织样本,分别使用qPCR和特异性探针底物分析基因表达以及CYP依赖性活性。对于所有研究的转录因子和细胞色素P450,肝脏中的mRNA表达和活性最高。在所有研究组织中均显示出CYP1A1和CYP3A的mRNA表达及活性。沿小肠和结肠,CYP1A1和CYP3A的mRNA表达及活性逐渐降低。结果表明,这与人类报道的情况相似,因此增加了猪作为人类模型的用途。

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