雷公藤甲素单次及多次给药对大鼠肝药酶活性的影响

目的:研究雷公藤甲素对大鼠肝药酶活性的影响。方法:对SD大鼠以雷公藤甲素(150、300、450μg·kg-1)灌胃给药,每天1次,给药1d或14d,分别测定细胞色素P450、细胞色素b5含量及红霉素N-去甲基酶(ERD)、二甲基亚硝胺脱甲基酶(NDMA)、甲氧基异唑脱甲基酶(MROD)、乙氧基异唑脱乙基酶(EROD)和戊氧基异唑脱烷基酶(PROD)活性;CYP3A和CYP2E1蛋白含量采用Westernblotting法分析。结果:单次灌胃雷公藤甲素对肝药酶活性及CYP2E1、CYP3A蛋白表达基本无影响;多次给予雷公藤甲素(450μg·kg-1,14d)能诱导NDMA活性,抑制ERD活性,轻度升高CYP2E1蛋白表达,显著降低CYP3A蛋白表达。结论:长期较高剂量给予雷公藤甲素能抑制CYP3A活性,轻度诱导CYP2E1活性。

Effect of Single and Multiple-dose Administration of Triptolide on the Activities of Drug-metabolism Enzymes in Rat Liver Microsome

OBJECTIVE： To investigate the effects of triptolide on the activities of drug-metabolism enzymes in rat liver microsome. METHODS： SD rats were given triptolide （150, 300, 450 ug.kg^- 1） via i.g. gtt once a day for 1 or 14 days. The contents of cytochrome P450, cytochrome b5 in rat liver mierosome and the activity of ERD, NDMA, MROD, EROD, PROD were assayed respectively. Western blotting was applied to test the protein expressions of CYP3A and CYP2E1. RESULTS： Single-dose administration of triptolide has no effect on the activity of drug-metabolism enzymes and the protein expression of CYP2E1 and CYP3A. multiple-dose administration of triptolide （450 ug. kg ^-1 14 d） induced the activity of NDMA and inhibited the activity of ERD while protein expression of CYP2E1 was increased slightly and protein expression of CYP3A decreased significantly. CONCLUSION： Multiple-dose administration of triptolide（450 ug.kg^- 1, 14 d） inhibite the activity of CYP3A but induce the activity of CYP2E1.