中文摘要：

目的：比较大鼠肝细胞在单层贴壁、胶原凝胶包埋和聚球体三种培养方式下药物代谢酶的活性及β-萘黄酮（BNF）对酶的诱导作用，考察组织化培养大鼠肝细胞的药物代谢能力。方法：大鼠肝细胞经三种培养方式培养一定时间后，分别加入非那西丁和7-羟基香豆素（7-HC），高效液相色谱法测定代谢产物对乙酰氨基酚、葡萄糖化7-羟基香豆素（7-HC GLUC）和硫酸化7-羟基香豆素（7-HC SULF）的浓度，分别用于表征Ⅰ、Ⅱ相药物代谢酶的活性。以BNF作为药物代谢酶的诱导剂，分别考察它对Ⅰ、Ⅱ相药物代谢酶的诱导情况。结果：单层贴壁培养肝细胞Ⅰ相药物代谢酶活性在第5天已检测不到，Ⅱ相药物代谢酶的活性在第7天已低于检测下限。在胶原凝胶包埋和聚球体两种培养方式下，大鼠肝细胞的Ⅰ和Ⅱ相酶活性在第7天还能保持初始值的32％～50％，且肝细胞聚球体的对乙酰氨基酚生成速率到第7天仍维持第1天的96％。肝细胞培养1～3d，肝细胞聚球体培养Ⅰ相药物代谢酶的活性比单层贴壁培养高2．7～3．9倍（P〈0．01，P〈0．05）。BNF处理后，三种培养模型的Ⅰ相酶的活性都有2．5倍左右的提高（P〈0．05），而Ⅱ相酶的活性增加并不明显。结论：在保持药物代谢酶活性方面，肝细胞的胶原凝胶包埋和聚球体培养方式比单层贴壁培养方式更优，可能成为研究药物代谢和药物相互作用更合适的体外模型。

英文摘要：

Objective： To investigate phase Ⅰ and phase Ⅱ enzyme activities in drug metabolism with tissue-like cultures of rat hepatocytes. Methods： The gel entrapment and spheroid culture of hepatocytes were used as tissue-like cultures and the monolayer culture was used as a control. The metabolism of phenacetin and 7-hydroxycoumarin（7-HC） was evaluated as the activities of phase Ⅰ and phase Ⅱ enzymes after incubated in medium for a period of time. The metabolites were assayed by HPLC. The hepatocytes were exposed to β-naphthoflavone （BNF,50 μmol · L^1） before the phase Ⅰ and phase Ⅱ enzyme activities were analyzed. Results： In monolayer culture, phase Ⅰ parameters decreased quickly and did not detected at d 5, and the phase Ⅱ enzyme activities were not detected at d 7. In other two models of tissue-like cultures, the activities of phase Ⅰ and phase Ⅱ enzyme maintained at 32%-50% of the initial value at d 7. Paracetanol formation rates in spheroid culture maintained at 96% of that at d 1. The phase Ⅰ enzyme activities of the spheroid culture were maintained from d 1 to d 3 at a level of 2.7-3.9- fold higher than the monolayer culture. After exposure to BNF the activities on phase Ⅰ enzyme increased by about 2.5-fold （P〈0.05） in all three culture models,while the increase in phase Ⅱ enzyme was not significa superior to the monolayer nt. Conclusion： The gel entrapment culture and spheroid culture are culture in maintenance of drug metabolic enzyme activities.