五味子乙素对CYP450药物代谢酶诱导作用的体外研究

Study on induction of cytochrome P450 enzymes by schisandrin B in vitro

目的研究五味子乙素对细胞色素P450(CYP450)酶活性和mRNA表达是否有诱导作用。方法采用底物法测定人肝原代细胞CYP1A2、CYP2B6和CYP3A4酶的活性,荧光定量PCR检测mRNA的表达。结果五味子乙素对CYP1A2和CYP3A4的酶活性均低于阳性对照的40%,高浓度的五味子乙素对CYP2B6的酶活性均高于阳性对照的40%;五味子乙素对CYP1A2的mRNA表达小于阴性对照的4倍,高浓度的五味子乙素对CYP2B6和CYP3A4的mRNA表达大于阴性对照的4倍。结论五味子乙素对CYP1A2和CYP3A4的酶活性没有诱导作用,对CYP2B6的酶活性有潜在诱导作用;五味子乙素对CYP1A2的mRNA表达没有诱导作用,对CYP2B6和CYP3A4的mRNA表达有潜在诱导作用。

Objective To study whether schisandrin B induced the enzyme activity and mRNA expression of cytochrome P450 enzymes.Methods The enzyme activity in human primary hepatocyte was evaluated with the probe substrates of CYP1A2, CYP2B6 and CYP3A4 enzyme, and the expression of mRNA was detected by fluorescence quantitative PCR. Results The enzyme activity in CYP1A2 and CYP3A4 was 40% lower than that of positive control, and the enzyme activity induced by high concentration of schisandrin B was 40% higher than that of the positive control in CYP2B6.The mRNA ex- pression in CYP1A2 was less than four times that of the negative control,and mRNA expression in CYP2B6 and CYP3A4 induced by high concentration of schisandrin B was four times greater than that of negative control.Conclusion Schisandrin B had no induced effect on the enzyme activity of CYP 1 A2 and CYP3A4, and potential induced effect on the enzyme activity of 2B6.Schisandrin B had no induced effect on mRNA expression of CYP 1A2, and potential induced effect on the mRNA expression of CYP2B6 and CYP3A4.