木犀草素对大鼠CYP450酶活力和mRNA表达的影响

目的 研究木犀草素对大鼠细胞色素P450（CYP450）酶活力和mRNA表达的影响。方法 SD大鼠随机分为实验组和对照组，连续灌胃木犀草素或水14 d后，同时给予探针药非那西丁、安非他酮、氯唑沙宗和咪达唑仑，并用LC-MS测定给药后不同时间点的血药浓度，计算药动学参数并评估CYP1A2、CYP2B1、CYP2E1和CYP3A1酶活力变化。此外，实时荧光定量PCR （RT-PCR）测定CYP450的mRNA表达水平。结果 实验组大鼠非那西丁、安非他酮、咪达唑仑的药动学参数与对照组相比具有显著性差异，推测木犀草素能诱导大鼠CYP1A2、CYP2B1和CYP3A1活力，而氯唑沙宗的药动学参数2组间没有显著性差异。RT-PCR实验发现，木犀草素能显著上调大鼠CYP1A2、CYP2B1和CYP3A1的mRNA水平，对CYP2E1没有影响。结论 木犀草素会上调CYP1A2、CYP2B1和CYP3A1酶活力及mRNA表达水平。

Effects of Luteolin on Activities and mRNA Expressions of Cytochrome P450 Enzymes in Rats

OBJECTIVE To investigate the effects of luteolin on activities and mRNA expressions of cytochrome P450 (CYP450) enzymes in rats. METHODS SD rats were randomly divided into test group and control group. After treatment with luteolin or water for 14 d, rats of control group and test group were given the mixture of four probes including phenacetin, bupropion, chlorzoxazone and midazolam. The plasma concentration of probes at a series of time-points after dosing were determined by liquid chromatography tandom mass spectrometry. The activities of CYP450s(CYP1A2, CYP2B1, CYP2E1, CYP3A1) were evaluated according to the pharmacokinetic parameters of corresponding probes. Real-time PCR was applied to assess the mRNA levels of CYP450s. RESULTS The pharmacokinetic parameters of phenacetin, bupropionand and midazolam from test group showed significant differences compared with control group, which indicated that luteolin induced CYP1A2, CYP2B1 and CYP3A1 activities. And no significant difference was found in pharmacokinetic parameters of chlorzoxazone from test group with control group. In addition, treatment with luteolin significantly up-regulated the mRNA expressions of CYP1A2, CYP2B1 and CYP3A1 whereas it had no impact on CYP2E1. CONCLUSION Luteolin can up-regulate the activities and mRNA expressions of CYP1A2, CYP2B1 and CYP3A1.