中文摘要：

目的采用孕烷受体-细胞色素 P450 3A4 （pregnane X receptor-cytochrome P450 3A4，PXR-CYP3A4）工程细胞株筛选复方丹参中诱导或抑制PXR-CYP3A4通路的化学成分。方法利用实验室构建的PXR-CYP3A4稳定转染人肝母细胞癌（human hepatoblastoma G2，HepG2）工程细胞株结合报告基因技术，筛选复方丹参中诱导或抑制PXR-CYP3A4通路的化学成分，并从酶活性水平进行确证。实验分为阳性对照组（RIF，10 μmol/L）、溶剂对照组（DMSO，0.1%）、药物处理各剂量组（人参皂苷Rc、Rf、Rb2、Rg2、F2、F1、Re，丹参酮Ⅰ，异龙脑5、10、25、50、100、200 μmol/L），每种药物设置6个复孔，加药36、48 及60 h后吸取细胞培养液上清，测定CYP3A4活性，计算诱导倍数。结果与溶剂对照组比较，人参皂苷Rc、Rf、Rb2、Rg2、F2、F1、Re，丹参酮Ⅰ，异龙脑50、100 μmol/L处理30、48和60 h时，诱导倍数均升高（P〈0.05），其中药物浓度200 μmol/L组处理48和60 h时，人参皂苷Rb2、Rg2、F1组诱导倍数均显著高于RIF阳性对照组（P〈0.05）。人参皂苷48 h时Rc、Rf、Rb2、F2、F1组CYP3A4酶活性提高（P〈0.05）。结论复方丹参中的人参皂苷Rc、Rf、Rb2、F2、 F1，丹参酮Ⅰ及异龙脑可以诱导CYP3A4酶。

英文摘要：

Objective To screen active components in Compound Danshen （CD） based on pregnane X receptor-cytochrome P450 3A4 （PXR-CYP3A4）. Methods By using PXR-CYP3A stable transfection human hepatoblastoma G2 （HepG2） cell lines engineering cell strain combined reporter genes technology, active components that induce or inhibit PXR-CYP3A4 paths in CD were screened, and confirmed at the level of enzymic activities. The experiment was divided into the positive control group （RIF 10μmol/L）, the DMSO group （DMSO 0.1%）, each dose of treatment groups （ginsenoside Rc, Rf, Rb2, Rg2, F2, F1, tanshinone I , isoborneol 5, 10,25, 50, 100, and 200 μmol/L; each with six duplicates）. Cells medium was removed 36, 48, and 60 h after treatment. The activity of CYP3A4 was then determined in the supernant and the fold induction was calculated. Results Compared with the DMSO group, the fold induction increased when ginsenoside Rc, Rf, Rb2, Rg2, F2, F1, tanshinone I , and isoborneol 50 and 100 μmol/L was respectively intervened for 36, 48, and 60 h （P 〈0.05）. When cells were treated with isoborneol 200 μmol/L for 48 and 60 h,the fold induction of ginsenoside Rb2, Rg2, and F1 was significantly higher than that of the RIF group （P 〈0.05）. Enzymic activity results showed that ginsenoside Rc, Rf, Rb2, F2, and F1 could increase the enzyme activity of CYP3A4 at 48 h （P 〈0.05）. Conclusion Ginsenoside Rc, Rf, Rb2, F2, F1, tanshinone I , and isoborneol in DC could induce CYP3A4 enzymes.