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从再生大鼠肝脏分离的肝细胞中细胞色素P450酶的体外诱导

In vitro induction of cytochrome P450 enzymes in hepatocytes isolated from the regenerating rat liver.

作者信息

Tamási Viola, Riedl Zsuzsanna, Dobozy Ottó, Falus András, Vereczkey László, Monostory Katalin

机构信息

Department of Biochemical Pharmacology, Chemical Research Center, Hungarian Academy of Sciences, P.O. Box 17, H-1525 Budapest, Hungary.

出版信息

Pol J Pharmacol. 2004 Jan-Feb;56(1):113-9.

PMID:15047985
Abstract

Partial hepatectomy results in the loss of cytochrome P450 enzymes. During regeneration, the levels of cytochrome P450 activities, apoproteins and mRNA are reduced. Our present study investigated CYP1A, CYP2E1 and CYP3A induction in the cells of rat liver regenerating for 1, 3, 7, or 14 days. Hepatocytes were isolated from regenerating liver of hepatectomized rats and treated with enzyme inducers: 3-methylcholanthrene, imidazole and dexamethasone. CYP1A enzymes of the cells isolated from regenerating liver were inducible by 3-methylcholanthrene. The rate of induction of the cells from 3-day regenerating liver by 3-methylcholanthrene was three times higher than that of the hepatocytes of sham-operated rats. Dexamethasone caused about two- or three-fold stronger elevation of CYP3A in the cells of 1-, 3- and 7-day regenerating liver than in hepatocytes of sham-operated animals. However, the degree of CYP2E1 induction by imidazole was the same (about 2.5-fold) at each regenerating time as it was detected in the hepatocytes of sham-operated animals. In conclusion, the inducibility of the cells was retained at each regenerating time, but the degree of induction showed some differences.

摘要

部分肝切除会导致细胞色素P450酶的丧失。在再生过程中,细胞色素P450活性、载脂蛋白和mRNA水平会降低。我们目前的研究调查了在肝切除后1、3、7或14天进行肝再生的大鼠肝脏细胞中CYP1A、CYP2E1和CYP3A的诱导情况。从肝切除大鼠的再生肝脏中分离出肝细胞,并用酶诱导剂处理:3-甲基胆蒽、咪唑和地塞米松。从再生肝脏中分离出的细胞中的CYP1A酶可被3-甲基胆蒽诱导。3-甲基胆蒽对3天再生肝脏细胞的诱导率比假手术大鼠的肝细胞高3倍。地塞米松使1、3和7天再生肝脏细胞中的CYP3A升高程度比假手术动物的肝细胞高约2至3倍。然而,咪唑对CYP2E1的诱导程度在每个再生时间点与假手术动物肝细胞中检测到的相同(约2.5倍)。总之,细胞的诱导能力在每个再生时间点都得以保留,但诱导程度存在一些差异。

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