目的:观察山奈酚和槲皮素两种银杏黄酮对细胞色素P450的影响。方法:原代培养大鼠肝细胞,接触0.1~10.0μmol/L的山奈酚或槲皮素,作用12h、24h和48h,用Nash法检测细胞色素P450同工酶一红霉素N-脱甲基酶(ENRD)和氨基比林N-脱甲基酶(ADM)的活性。分别以红霉素(10.0μmol/L)和二甲基亚砜(DMSO)作为阳性对照和溶剂对照。结果:0.1、1.0和10.0μmol/L山奈酚作用24h,ENRD酶活性分别为(0.088±0.008)、(0.074±0.006)和(0.041±0.003)μmol/(mg·min^-1);槲皮素相同浓度和作用时间处理的ENRD酶活性分别为(0.082±0.007)、(0.063±0.007)和(0.034±0.005)μmol/(mg·min^-1)。其中1.0和10.0μmol/L山奈酚和槲皮素处理的肝细胞ENRD酶活性都显著低于溶剂对照组(0.085±0.011)μmol/(mg·min^-1),且呈剂量-效应关系(P〈0.01)。10μmol/L山奈酚处理细胞12h和48h后,ENRD酶活性为(0.053±0.006)和(0.037±0.007)μmol/(mg·min^-1);10μmol/L槲皮素处理细胞12h和48h后,ENRD酶活性为(0.067±0.005)和(0.032±0.004)μmol/(mg·min^-1),都具有明显的时间-效应关系(P〈0.01)。山奈酚只有在10μmol/L浓度下作用24h对ADM活性出现抑制,槲皮素对ADM活性没有明显影响。结论:在本实验条件下,山奈酚和槲皮素能明显抑制大鼠肝细胞ENRD活性;山奈酚在10μmol/L浓度下能轻度抑制ADM,而槲皮素对ADM活性没有明显的抑制作用。
Objective: To observe the effects cytochrome P450 in rat hepatocytes. Methods: of kaempferol and quercetin on the activity of Primarily cultured rat hepatocytes were exposed to kaempferol or quercetin in concentrations of 0. 1,1,10 μmol/L for 12 h, 24 h and 48 h. Hepatocytes CYP isoemzymes-erythromycin N-demethylase (ERND) and aminopyrine Ndemethylase (ADM) activities were determined by Nash methods. Erythromycin (10μmol/L)was as positive control and DMSO (0.1%) as solvent control. Results: Kaempferol and quercetin inhibited ENRD activity in a dose and time-dependent manner. In dose-response study,the ENRD activities in kaempferol (0.1,1 and 10 μmol/L) treated groups were (0. 088± 0. 008), (0. 074±0. 006) and (0. 041±0. 003)μmol/(mg·min^-1) ,respectively. ENRD activity in quercetin treated groups at the same concentrations were (0. 082±0. 007), (0. 063±0. 007) and (0.034±0.005)μmol/(mg·min^-1),respectively. In time-courses study,the ENRD activity exposed to 10 μmol/L kaempferol or quercetin for 12 h and 48 h were (0. 053±0. 006) and (0. 037±0. 007)μmol/(mg·min^-1),or (0. 067±0. 005) and (0. 032±0. 004)μmol/(mg·min^-1). ADM activity was inhibited only by kaempferol in 10 mol/L at 24 h,but was not significantly altered by quercetin at any concentration tested. Conclusion.-In the present condition, kaempferol and quercetin act as potential CYP3A4 inhibitors as they can significantly inhibit ENRD in primarily cultured rat hepatocytes.