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首页> 外文OA文献 >Effects of dietary fish oil on cytochrome P450 3A expression in the liver of SHR/NDmcr-cp (cp/cp) rats, an animal model for metabolic syndrome
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Effects of dietary fish oil on cytochrome P450 3A expression in the liver of SHR/NDmcr-cp (cp/cp) rats, an animal model for metabolic syndrome

机译：食用鱼油对SHR / NDmcr-cp（cp / cp）大鼠（代谢综合征的动物模型）肝脏中细胞色素P450 3A表达的影响

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Pathophysiological and nutritional conditions often affect the expression of drug-metabolizing enzymes. SHR/NDmcr-cp (cp/cp) rats (SHR/NDcp) are highly suitable as a metabolic syndrome (MS) model. Nevertheless, little is known about the expression profile of cytochrome P450 (CYP) in the liver of SHR/NDcp. We thus attempted to clarify the expression profile of CYP genes and the effect of fish oil (FO) on this profile in the liver of SHR/NDcp. Lower levels of CYP3A2 mRNA and CYP3A activity (testosterone 6β-hydroxylation) were distinctive features in SHR/NDcp compared with their controls (Wistar Kyoto rats (WKY), spontaneously hypertensive rats (SHR), stroke-prone SHR and lean littermates of SHR/NDcp). Differently from CYP3A2, the expression of other CYP isoforms was largely unchanged in SHR/NDcp. The changes in CYP profile observed in SHR/NDcp are similar to those of patients with diabetes and simple hepatic steatosis. Feeding on FO at a high dose (18.8% in the diet) upregulated CYP3A2 gene expression and CYP3A activity in the liver; the extent of these increases was greater in SHR/NDcp than in WKY and lean littermates of SHR/NDcp. This effect was not observed with FO at a normal dose (5% in the diet). These results indicate that, in the context of the CYP profile, SHR/NDcp is an animal model that is suitable for studying MS and imply that FO intake is critical in determining the efficacy or adverse effects of drugs in patients with MS.
机译：病理生理和营养状况通常会影响药物代谢酶的表达。 SHR / NDmcr-cp（cp / cp）大鼠（SHR / NDcp）非常适合作为代谢综合征（MS）模型。但是，关于SHR / NDcp肝脏中细胞色素P450（CYP）的表达情况知之甚少。因此，我们试图阐明CYP基因的表达谱以及鱼油（FO）在SHR / NDcp肝脏中对该谱的影响。与对照组（Wistar Kyoto大鼠（WKY），自发性高血压大鼠（SHR），易发中风的SHR和SHR /瘦肉仔猪）相比，SHR / NDcp的CYP3A2 mRNA和CYP3A活性水平较低（睾丸激素6β-羟基化）具有明显特征。 NDcp）。与CYP3A2不同，其他CYP亚型在SHR / NDcp中的表达基本没有变化。在SHR / NDcp中观察到的CYP谱变化与糖尿病和单纯性肝脂肪变性患者相似。高剂量（饮食中为18.8％）摄入FO可上调肝脏中CYP3A2基因的表达和CYP3A的活性。 SHR / NDcp的增加幅度大于WKY和SHR / NDcp的瘦仔猪。正常剂量（饮食中为5％）的FO未观察到这种效果。这些结果表明，在CYP谱的背景下，SHR / NDcp是一种适合研究MS的动物模型，并暗示FO摄入对于确定MS患者的药物疗效或不良反应至关重要。

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