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大黄素对大鼠肝脏CYP450酶的诱导研究
引用本文:王青秀,雷荣辉,吴纯启,廖明阳,肖小河,王全军. 大黄素对大鼠肝脏CYP450酶的诱导研究[J]. 现代药物与临床, 2015, 38(2): 147-150
作者姓名:王青秀  雷荣辉  吴纯启  廖明阳  肖小河  王全军
作者单位:军事医学科医学院毒物药物研究所, 抗毒药物与毒理学国家重点实验室(军事医学科学院), 国家北京药物安全评价研究中心, 北京 100850;北京市海淀区卫生局卫生监督所, 北京 100037;军事医学科医学院毒物药物研究所, 抗毒药物与毒理学国家重点实验室(军事医学科学院), 国家北京药物安全评价研究中心, 北京 100850;西安交通大学医学部公共卫生学院, 西安 710061;军事医学科医学院毒物药物研究所, 抗毒药物与毒理学国家重点实验室(军事医学科学院), 国家北京药物安全评价研究中心, 北京 100850;军事医学科医学院毒物药物研究所, 抗毒药物与毒理学国家重点实验室(军事医学科学院), 国家北京药物安全评价研究中心, 北京 100850;解放军302医院全军中药研究所, 北京 100039;军事医学科医学院毒物药物研究所, 抗毒药物与毒理学国家重点实验室(军事医学科学院), 国家北京药物安全评价研究中心, 北京 100850
基金项目:重大新药创制科技重大专项(2013ZX09302303, 2012ZX09301-003-001-008)
摘    要: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。

关 键 词:大黄素  细胞色素P450  红霉素脱甲基酶  氨基比啉-N-脱甲基酶  CYP1A  CYP2B  CYP2E1
收稿时间:2014-11-03

Induction of cytochrome P450 enzymes by emodin in liver tissue of rats
WANG Qing-xiu,LEI Rong-hui,WU Chun-qi,LIAO Ming-yang,XIAO Xiao-he and WANG Quan-jun. Induction of cytochrome P450 enzymes by emodin in liver tissue of rats[J]. Drugs & Clinic, 2015, 38(2): 147-150
Authors:WANG Qing-xiu  LEI Rong-hui  WU Chun-qi  LIAO Ming-yang  XIAO Xiao-he  WANG Quan-jun
Affiliation:National Beijing Center for Drug Safety Evaluation and Research, State key laboratory of Toxicology and Medical Countermeasures (Academy of Military Medical Sciences), Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;The Bureau for Health Inspection and Supervision of Haidian District, Beijing 100037, China;National Beijing Center for Drug Safety Evaluation and Research, State key laboratory of Toxicology and Medical Countermeasures (Academy of Military Medical Sciences), Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;School of Public Health, Xi'an Jiaotong University Health Science Center of Xi'an Jiaotong University, Xi'an 710061, China;National Beijing Center for Drug Safety Evaluation and Research, State key laboratory of Toxicology and Medical Countermeasures (Academy of Military Medical Sciences), Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;National Beijing Center for Drug Safety Evaluation and Research, State key laboratory of Toxicology and Medical Countermeasures (Academy of Military Medical Sciences), Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China;Department of Pharmacy, 302 Hospital of PLA, Beijing 100039, China;National Beijing Center for Drug Safety Evaluation and Research, State key laboratory of Toxicology and Medical Countermeasures (Academy of Military Medical Sciences), Institute of Pharmacology and Toxicology, Academy of Military Medical Sciences, Beijing 100850, China
Abstract: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.
Keywords:emodin  cytochrome P450 enzyme  CYP3A  aminopyrine N-demethylase  CYP1A  CYP2B  CYP2E1
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