对基因定义大鼠品系肝细胞中药物生物转化的初步评估。

A preliminary evaluation of drug biotransformation in hepatocytes of genetically defined rat strains.

作者信息

Hynie S, Kren V, Bílá V, Mráz M, Gaier N, Kameníková L, Farghali H

机构信息

Institute of Pharmacology, First Medical Faculty, Charles University, Prague, Czech Republic.

出版信息

Physiol Res. 1994;43(2):131-5.

PMID:7918339

Abstract

This study was directed to use the genetically developed isoprenaline-sensitive (S), isoprenaline-resistant (R) and spontaneous hypertensive rats (SHR) as standard diseased animal models for in vitro liver function evaluation of drug biotransformation. Hepatic hexobarbital hydroxylase and glutathione transferase (GST) were evaluated by using hexobarbital and 1-chloro-2,4-dinitrobenzene (CDNB) as substrates, at concentrations of 0.21 mmol/l and 1 mmol/l, respectively. The assay was conducted by using isolated hepatocytes in suspension and hepatocytes in a bioreactor configuration. The data demonstrate that there are certain cellular pharmacokinetic differences in hexobarbital hydroxylase and GST activities in hepatocytes obtained from Wistar, SHR, R and S strains which can be better demonstrated, when using the model of perfused and immobilized hepatocytes.

摘要

本研究旨在利用基因培育的对异丙肾上腺素敏感（S）、对异丙肾上腺素抵抗（R）的大鼠以及自发性高血压大鼠（SHR）作为标准疾病动物模型，用于体外评估药物生物转化的肝功能。分别以0.21 mmol/l和1 mmol/l的浓度，使用己巴比妥和1-氯-2,4-二硝基苯（CDNB）作为底物，评估肝脏己巴比妥羟化酶和谷胱甘肽转移酶（GST）。该测定通过使用悬浮的分离肝细胞和生物反应器配置中的肝细胞来进行。数据表明，从Wistar、SHR、R和S品系获得的肝细胞中，己巴比妥羟化酶和GST活性存在一定的细胞药代动力学差异，当使用灌注和固定化肝细胞模型时，这种差异能得到更好的体现。