胶原凝胶包埋培养大鼠肝细胞用于药物代谢地研究.pdfVIP

胶原凝胶包埋培养大鼠肝细胞用于药物代谢的研究1 1 2 1 裘虹霞 张国亮 孟琴 (1 浙江大学材料化工学院化学工程与生物化学工程系， 杭州310027 2 浙江工业大学生物工程与环境工程学院，杭州310014) 摘 要 本实验研究了微型中空纤维反应器中胶原凝胶包埋培养大鼠肝细胞用于药物代谢的 情况。以非那西汀的代谢表征Ⅰ相酶活，以7-HC 的代谢表征Ⅱ相酶活。以BNF 作为诱导剂， 检测BNF 对Ⅰ相酶活的诱导。结果发现，Ⅰ相和Ⅱ相的酶活在第 7 天还能保持初始值的35 ％。经过BNF 诱导后，所检测的Ⅰ相酶的活性增加了2.4 倍左右。本实验结果提示了微型中 空纤维反应器中肝细胞的凝胶包埋培养比较适合用于药物代谢及药物之间相互作用的研究。 关键词 大鼠肝细胞；药物代谢；凝胶包埋培养；单层贴壁培养 Gel Entrapment Culture of Rat Hepatocytes for Drug Metabolism 1 2 1 Hongxia Qiu , Guoliang Zhang , Qin Meng 1 （ Department of Chemical and Biological Engineering, Zhejiang University, Hangzhou, Zhejiang 310027 2 Institute Biological and Environment Engineering, Zhejiang University of Technology, Hangzhou , Zhejiang 310032 ） To estimate the drug metabolism of the gel entrapment cultures of rat hepatocytes ，the activity of phase Ⅰ and Ⅱ enzymes in the biotransformation of drugs and their inducibility by β-naphthoflavone(BNF) were studied in the gel entrapment of hepatocytes in hollow fiber chambers. The metabolism of phenacetin and 7-hydroxycoumarin(7-HC) were respectively evaluated as the activities of phase Ⅰand phase Ⅱenzymes. For investigate the inducibility of BNF （50 μmol/L ）, the hepatocytes were exposed to BNF for 48 h before the metabolism of phase Ⅰparameter were analyzed. Phase Ⅰand phase Ⅱ enzyme activities of gel entrapment kept about 35% at the 7th day. After β-naphthoflavone treatment, the parameters mentioned in phase Ⅰ were increased about 2.4-fold. The results show that the gel entrapment cultures of hepatocytes in micro hollow fiber reactor may be suited for drug metabolism and drug-drug interaction investigation. 前言 肝实质细胞具有完整的药物代谢酶体系，是药物生物转化的主要场所，因此原代肝细胞 常被用于体外药物代谢的