目的 探討大黃素對大鼠肝臟細(xì)胞色素P450酶(CYP450)及其主要亞型的影響。方法 20只雄性SD大鼠, 隨機(jī)分成4組, 每組5只, 分別為溶劑對照組, 170、500和1 500 mg/kg大黃素染毒組, 大黃素蒸餾水混懸后連續(xù)經(jīng)口給藥16 d, 結(jié)束后次日取大鼠肝臟組織制作微粒體, 分別采用CO還原差示光譜法、分光光度法及化學(xué)發(fā)光法檢測大鼠肝臟微粒體總CYP450水平, 紅霉素脫甲基酶(CYP3A)、氨基比啉-N-脫甲基酶, CYP1A、CYP2B和CYP2E1酶活性變化。結(jié)果 大黃素連續(xù)經(jīng)口給藥16 d, 能夠引起大鼠肝臟微粒體總CYP450顯著升高、可輕度誘導(dǎo)CYP3A、CYP1A、CYP2E1和CYP2B酶, 500 mg/kg劑量組最明顯。結(jié)論 大黃素對大鼠肝臟中CYP3A、CYP1A、CYP2B和CYP2E1酶均有誘導(dǎo)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.

重大新藥創(chuàng)制科技重大專項(2013ZX09302303, 2012ZX09301-003-001-008)