目的 探讨大黄素对大鼠肝脏细胞色素P450酶(CYP450)及其主要亚型的影响。方法 20只雄性SD大鼠, 随机分成4组, 每组5只, 分别为溶剂对照组, 170、500和1 500 mg/kg大黄素染毒组, 大黄素蒸馏水混悬后连续经口给药16 d, 结束后次日取大鼠肝脏组织制作微粒体, 分别采用CO还原差示光谱法、分光光度法及化学发光法检测大鼠肝脏微粒体总CYP450水平, 红霉素脱甲基酶(CYP3A)、氨基比啉-N-脱甲基酶, CYP1A、CYP2B和CYP2E1酶活性变化。结果 大黄素连续经口给药16 d, 能够引起大鼠肝脏微粒体总CYP450显著升高、可轻度诱导CYP3A、CYP1A、CYP2E1和CYP2B酶, 500 mg/kg剂量组最明显。结论 大黄素对大鼠肝脏中CYP3A、CYP1A、CYP2B和CYP2E1酶均有诱导作用。

Objective To explore the effects of emodin on cytochrome P450 enzyme (CYP450) and elucidate the toxicity mechanism of emodin. Methods Twenty male SD rats were randomly divided into four groups. The extracts of the liver tissues of rats treated with emodin at different doses (170, 500, 1 500 mg/kg for 16 d) were in preparation of microsomes, the activities of total CYP450, CYP3A, aminopyrine N-demethylase, CYP1A, CYP2B, and CYP2E1 were respectively determined by the reduction of CO difference spectroscopy, spectrophotometer, and chemiluminescence method. Results Induction of the total cytochrome P450 enzyme, CYP3A, CYP1A, CYP2E1, and CYP2B were observed in the liver tissues of rats treated with emodin for 16 d, the induction effect was most obvious in the liver tissues of rats in 500 mg/kg group. Conclusion Emodin could induce the cytochrome P450 enzyme including CYP3A, CYP1A, CYP2B, and CYP2E1 in the liver tissues of rats.

重大新药创制科技重大专项(2013ZX09302303, 2012ZX09301-003-001-008)