基于人肝微粒体CYP1A2亚型酶研究丹红注射液与阿司匹林的相互作用  

Interaction between Danhong injection and aspirin based on human liver microsome CYP1A2

作　　者：李学林[1,2] 张帆[1] 李伟霞[2] 曹英杰[2] 王晓艳[2] 张书琦 唐进法[1,2] LI Xue-lin;ZHANG Fan;LI Wei-xia;CAO Ying-jie;WANG Xiao-yan;ZHANG Shu-qi;TANG Jin-fa(Henan University of Traditional Chinese Medicine, Zhengzhou 450008, China;Department of Pharmacy, the First Affiliated Hospital of Henan University of Traditional Chinese Medicine, Zhengzhou 450000, China)

机构地区：[1]河南中医药大学,郑州450008 [2]河南中医药大学第一附属医院,郑州450000

出　　处：《中国新药杂志》2018年第9期1034-1039,共6页Chinese Journal of New Drugs

基　　金：2016年度河南省高等学校重点科研项目(17A360001;17A360005);河南中医药大学研究生科研苗圃工程项目(MPYJS2017-07)

摘　　要：目的:基于丹红注射液、阿司匹林单用及其联合使用对人肝微粒体CYP1A2亚型酶活性的影响,探讨丹红注射液与阿司匹林的代谢性相互作用,为临床合理用药提供依据。方法:以人肝微粒体CYP1A2为载体,非那西丁为探针底物,其代谢产物对乙酰氨基酚为检测指标,采用超高效液相色谱-四级杆-飞行时间-串联质谱(UPLC-Q-TOF-MS/MS)中多反应监测(MRM)模式测定对乙酰氨基酚的浓度,比较评价丹红注射液(0.4%,0.8%和1.6%)、阿司匹林(20,60和100 mg)不同剂量单独给药及其联合给药(对其中一个药物进行预孵育一段时间后再加入另一药物)对CYP1A2亚型酶活性的影响。结果:丹红注射液对CYP1A2亚型酶活性有抑制作用,抑制类型为混合型。与空白对照组比较,丹红注射液低、中、高剂量均对CYP1A2亚型酶活性有显著抑制作用;但阿司匹林低、中、高剂量均对CYP1A2亚型酶活性无明显作用。与丹红注射液低、中、高剂量的单独给药组比较,丹红注射液3个剂量分别与低、中、高剂量的阿司匹林联合给药组对CYP1A2亚型酶活性无显著性影响。小剂量阿司匹林对CYP1A2亚型酶活性无明显作用。与阿司匹林低、中剂量的单独给药组比较,阿司匹林低、中剂量与丹红注射液的中、高剂量联合给药组对CYP1A2亚型酶活性有显著性作用;与阿司匹林高剂量的单独给药组比较,阿司匹林高剂量与低、中、高剂量的丹红注射液联合给药组对CYP1A2亚型酶活性均有显著性影响。结论:阿司匹林与丹红注射液联合使用对CYP1A2亚型酶活性有一定相互作用,并与两者的用药先后顺序具有相关性。Objective： To investigate the effects of Danhong injection and aspirin used alone or in combination on activity of human liver microsomal CYP1 A2 subtype,and the metabolic interaction of Danhong injection and aspirin,so as to provide evidence for rational use of drugs in clinic. Methods： Human liver microsome CYP1 A2 was used as the carrier,and phenacetin as probe substrate. The product of acetaminophen was selected as the index of detection. Concentration of acetaminophen was determined by the TOF-MRM detection mode in the UPLC-QTOF-MS/MS. The effects of Danhong injection(0. 4%,0. 8%,1. 6%） and aspirin(20 mg,60 mg,100 mg）alone or in combination on CYP1 A2 activity were compared. In the case of combination,one of the drugs were preincubated for a period of time,thereafter another drug was added. Results： Danhong injection remarkably inhibited the activity of CYP1 A2 in vitro in a mixed-type inhibition manner. Compared with the blank control group,Danhong injection(0. 4%,0. 8%,1. 6%） had a significant inhibitory effect on the enzyme activity of CYP1 A2 subtype; but aspirin(20 mg,60 mg,100 mg） had no obvious effect on the enzyme activity of CYP1 A2 subtype.Compared with Danhong injection alone,the combination with aspirin did not affect the effect of Danhong injection(0. 4%,0. 8%,1. 6%） on the activity of CYP1 A2 subtype. Low-dose aspirin(20 mg） had no effect on CYP1 A2 activity. Compared with aspirin(20 and 60 mg） alone,aspirin(20 mg,60 mg） combined with Danhong injection(0. 8%,1. 6%） significantly inhibited the activity of CYP1 A2 subtype. Compared with high dose aspirin(100 mg）alone,aspirin(100 mg） combined with Danhong injection(0. 4%,0. 8%,1. 6%） significantly inhibited the activity of CYP1 A2 subtype. Conclusion： The combination of Danhong injection with aspirin has certain interaction on the enzyme activity of CYP1 A2 subtype,and has a correlation with the addition sequence of the two drugs. This experiment provides a reference for scientific and rational combination use of dr

关 键 词：丹红注射液 阿司匹林 人肝微粒体 细胞色素P450酶 相互作用 

分 类 号：R285[医药卫生—中药学] R932[医药卫生—中医学]