射干异黄酮有效成分对肝药酶亚型作用研究
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摘要
目的:运用"鸡尾酒"探针药物法,探讨射干总苷和射干总苷元对肝药酶亚型的作用。方法:以地西泮为内标物,采用"鸡尾酒"探针技术,检测咖啡因、美托洛尔、氯唑沙宗、甲苯磺丁脲四种探针药物在大鼠血清代谢中的含量变化,通过HPLC方法得出血药浓度数据,绘制平均药-时曲线,计算药代动力学参数。结果:实验组咖啡因(CYP1A2)的AUC明显增大(P <0. 05),经t检验,结果具有统计学意义;实验组美托洛尔(CYP2D6)的半衰期明显减小(P <0. 05),经过t检验,结果具有统计学意义。结论:射干总苷和射干总苷元对CYP1A2酶具有抑制作用,对CYP2D6酶具有诱导作用。
Objective: To study the effects of total tectoridin and total tectorigenin on hepatic enzyme subtype by cooktail probe approach. Methods: The contents of caffeine,metoprolol,chlorzoxazone and tolbutamide in serum were measured by using cocktail probe technique with diazepam as internal standard. The plasma concentrations of the different probe drugs were determined by HPLC. The mean drug-time curve is plotted and we calculated the pharmacokinetic parameters. Results: In experimental group,the AUC of caffeine significantly increased than those in control group. The results were statistically significant by t test.. The half life of metoprolol significantly decreased than those in control group. The results were statistically significant by t test. Conclusion:Total tectoridin and total tectorigenin can inhibit the metabolic activities of CYP1 A2 and include the metabolic activities of CYP2 D6.
Objective: To study the effects of total tectoridin and total tectorigenin on hepatic enzyme subtype by cooktail probe approach. Methods: The contents of caffeine,metoprolol,chlorzoxazone and tolbutamide in serum were measured by using cocktail probe technique with diazepam as internal standard. The plasma concentrations of the different probe drugs were determined by HPLC. The mean drug-time curve is plotted and we calculated the pharmacokinetic parameters. Results: In experimental group,the AUC of caffeine significantly increased than those in control group. The results were statistically significant by t test.. The half life of metoprolol significantly decreased than those in control group. The results were statistically significant by t test. Conclusion:Total tectoridin and total tectorigenin can inhibit the metabolic activities of CYP1 A2 and include the metabolic activities of CYP2 D6.
引文
[1]呼自顺,徐津,李芹,等.“鸡尾酒”探针药物法评价苦参对大鼠的CYP450不同亚型体内代谢活性[J].中国医药学杂志,2013,33(21):1775-1778.
[2]朱倩,李俊,汤文建.中药对细胞色素P450酶活性影响及研究方法进展[J].安徽医药,2013,17(9):1457-1461.
[3]Liu XQ,Zhao Y,Li D,et al. Metabolism and metabolic inhibition of clinipine in human live rmicrosomes[J]. Acta Pharmacologica Sinica,2003,24(1):263-268.
[4]李文东,马辰.药物体外肝代谢研究进展[J].中国药学杂志,2003,38(10):737-740.
[5]周璐,乔静怡,金若敏.精密肝切片技术在药物研究中的应用[J].中成药,2013,35(6):1292-1295.
[6]候从颂,杨志宏,孙晓波.“cocktail”探针药物法及其在研究中药对细胞色素P450影响中的应用进展[J].中国药理学与毒理学杂志,2013,27(3):445-450.
[7]张杰,曾铖,常义生,等.射干化学成分研究[J].安徽农业科学,2015,43(24):57-59.
[8]国家药典委员会.中华人民共和国药典:2015年版一部[S].北京:中国医药科技出版社,2015:285.
[9]汪天青,张颖,尤献民,等.射干古今方药历史应用考证[J].中华中医药学刊,2016,34(11):2728-2731.
[10]卞娅,刘孟生,张丽媛,等.射干、鸢尾不同部位6种活性成分定量分析及抗炎作用初探[J].中国中药杂志,2018,43(1):119-122.
[11]王迪.米泔水制射干与射干对比研究[D].沈阳:辽宁中医药大学,2017.
[12]李锁.堇竹叶制射干炮制目的研究[D].沈阳:辽宁中医药大学,2017.
[13]林浩,林晖,黄鹏,等. Cocktail探针法测定细辛与藜芦配伍对大鼠肝细胞色素P450亚酶活性的影响[J].中药材,2014,37(7):1251-1254.
[14]Sharma A,Pilote S,Belanger PM,et al. A convenient five-drug cocktail for the assessment of major drugmetabolizing enzymes:a pilot study[J]. Br J Clin Pharmacol,2004,58:288-297.
[15]陈建龙,张玉玲,董宇,等. Cocktail探针药物法评价小檗碱对肝微粒体CYP450酶的抑制作用[J].中国中药杂志,2013,38(12):2009-2014.
[2]朱倩,李俊,汤文建.中药对细胞色素P450酶活性影响及研究方法进展[J].安徽医药,2013,17(9):1457-1461.
[3]Liu XQ,Zhao Y,Li D,et al. Metabolism and metabolic inhibition of clinipine in human live rmicrosomes[J]. Acta Pharmacologica Sinica,2003,24(1):263-268.
[4]李文东,马辰.药物体外肝代谢研究进展[J].中国药学杂志,2003,38(10):737-740.
[5]周璐,乔静怡,金若敏.精密肝切片技术在药物研究中的应用[J].中成药,2013,35(6):1292-1295.
[6]候从颂,杨志宏,孙晓波.“cocktail”探针药物法及其在研究中药对细胞色素P450影响中的应用进展[J].中国药理学与毒理学杂志,2013,27(3):445-450.
[7]张杰,曾铖,常义生,等.射干化学成分研究[J].安徽农业科学,2015,43(24):57-59.
[8]国家药典委员会.中华人民共和国药典:2015年版一部[S].北京:中国医药科技出版社,2015:285.
[9]汪天青,张颖,尤献民,等.射干古今方药历史应用考证[J].中华中医药学刊,2016,34(11):2728-2731.
[10]卞娅,刘孟生,张丽媛,等.射干、鸢尾不同部位6种活性成分定量分析及抗炎作用初探[J].中国中药杂志,2018,43(1):119-122.
[11]王迪.米泔水制射干与射干对比研究[D].沈阳:辽宁中医药大学,2017.
[12]李锁.堇竹叶制射干炮制目的研究[D].沈阳:辽宁中医药大学,2017.
[13]林浩,林晖,黄鹏,等. Cocktail探针法测定细辛与藜芦配伍对大鼠肝细胞色素P450亚酶活性的影响[J].中药材,2014,37(7):1251-1254.
[14]Sharma A,Pilote S,Belanger PM,et al. A convenient five-drug cocktail for the assessment of major drugmetabolizing enzymes:a pilot study[J]. Br J Clin Pharmacol,2004,58:288-297.
[15]陈建龙,张玉玲,董宇,等. Cocktail探针药物法评价小檗碱对肝微粒体CYP450酶的抑制作用[J].中国中药杂志,2013,38(12):2009-2014.