天然冰片对大鼠细胞色素P450四种亚型活性的影响

中国临床药理学与治疗学 ›› 2013, Vol. 18 ›› Issue (2): 121-127.

• 基础研究 • 下一篇

天然冰片对大鼠细胞色素P450四种亚型活性的影响

吴淳¹, 高静雯¹, 姚美村¹, 侯雪英¹, 周玉婷¹, 邓雪姣¹, 廖琼峰², 谢智勇¹

¹中山大学药学院,广州 510006,广东;
²广州中医药大学中药学院,广州 510006,广东

收稿日期:2012-09-21 修回日期:2012-09-21 发布日期:2013-02-28
通讯作者: 谢智勇,通信作者,男,博士,副教授,硕士生导师,研究方向:中药药代动力学。 Tel: 020-39943047 E-mail: xiezy2074@yahoo.com
作者简介:吴淳,女,在读硕士研究生,研究方向:中药药代动力学。 Tel: 13533723272 E-mail: wuchunchzx@163.com
基金资助:
国家自然科学基金面上项目(81173564,81274028); 中山大学青年教师培育项目(2010060)

Effect of natural borneol on the activities of cytochrome p450 isoforms in rats

WU Chun¹, GAO Jing-wen¹, YAO Mei-cun¹, HOU Xue-ying¹, ZHOU Yu-ting¹, DENG Xue-jiao¹, LIAO Qiong-feng², XIE Zhi-yong¹

¹School of Pharmaceutical Sciences, Sun Yat-sen University, Guangzhou 510006, Guangdong, China;
²School of Chinese Materia Medica, Guangzhou University of Chinese Medicine, Guangzhou 510006, Guangdong, China

Received:2012-09-21 Revised:2012-09-21 Published:2013-02-28

摘要/Abstract

摘要： 目的: 用Cocktail探针药物法研究天然冰片对大鼠细胞色素P450 四种亚型CYP1A2、CYP2C6/11、CYP2E1 和CYP3A 活性的影响。方法: 将大鼠随机分为2组,给药组灌胃给予天然冰片-0.8% CMC-Na混悬液,剂量 90 mg/kg,对照组灌胃给予不含药物的 0.8% CMC-Na溶液,每天1次,连续 7 d。于第8天,两组大鼠均尾静脉注射混合探针药物溶液(茶碱 10 mg/kg、甲苯磺丁脲 2.5 mg/kg、氯唑沙宗 10 mg/kg、氨苯砜 5 mg/kg),眼内眦静脉采血,超高效液相色谱法检测各探针药物的血药浓度,采用WinNonlin 5.0.1 计算药代动力学参数。结果: 与对照组相比,天然冰片组中甲苯磺丁脲的t_1/2、AUC_0-t、AUC_0-∞和MRT_0-∞明显减小,两组之间的差异具有统计学意义(P<0.05);而两组之间茶碱、氯唑沙宗和氨苯砜的药代动力学参数则没有明显差异。结论: 天然冰片对大鼠CYP2C6/11的活性具有诱导作用,对CYP1A2、CYP2E1和CYP3A活性无显著影响。

关键词: 天然冰片, 细胞色素P450, Cocktail探针药物法

Abstract: AIM: To study the effect of natural borneol on the activities of cytochrome P450 enzymes CYP1A2, CYP2C6/11, CYP2E1 and CYP3A by a cocktail approach in rats. METHODS: The rats were randomly divided into two groups.One group of rats were treated with natural borneol suspension containing 0.8% CMC-Na (90 mg/kg) by intragastric injection once a day for 7 days.At the same time, the rats in the other group received 0.8% CMC-Na solution serving as control group.On the 8th day, all rats in each group were intravenously injected with cocktail probe drugs (10 mg/kg theophylline, 2.5 mg/kg tolbutamide, 10 mg/kg chlorzoxazone, 5 mg/kg dapsone).Blood samples were drawn into heparinized tubes at different time points.The plasma concentration of probe drugs were determined by ultra performance liquid chromatography (UPLC) and the main pharmacokinetic parameters were calculated by WinNonlin 5.0.1. RESULTS: In natural borneol group, the t_1/2, AUC_0-t, AUC_0-∞ and MRT_0-∞ of tolbutamide were significantly lower than those in Control group (P<0.05). There were no significant differences in the pharmacokinetic parameters of theophylline, chlorzoxazone and dapsone between control group and natural borneol group.CONCLUSION: Natural borneol can induce the activity of CYP2C6/11, but has no influence on the activities of CYP1A2, CYP2E1 and CYP3A.

Key words: Natural borneol, Cytochrome P450, Probe cocktail

中图分类号:

R969.1

吴淳, 高静雯, 姚美村, 侯雪英, 周玉婷, 邓雪姣, 廖琼峰, 谢智勇. 天然冰片对大鼠细胞色素P450四种亚型活性的影响[J]. 中国临床药理学与治疗学, 2013, 18(2): 121-127.

WU Chun, GAO Jing-wen, YAO Mei-cun, HOU Xue-ying, ZHOU Yu-ting, DENG Xue-jiao, LIAO Qiong-feng, XIE Zhi-yong. Effect of natural borneol on the activities of cytochrome p450 isoforms in rats[J]. Chinese Journal of Clinical Pharmacology and Therapeutics, 2013, 18(2): 121-127.

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天然冰片对大鼠细胞色素P450四种亚型活性的影响

Effect of natural borneol on the activities of cytochrome p450 isoforms in rats

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