3种抗心血管病中成药对大鼠肝微粒体CYP450 4种亚型的体外活性影响研究  

Effects of three Chinese Patent Medicines Against Cardiovascular Disease on the in Vitro Activity of four Subtypes of Liver Microsomal Cytochrome P450 in Rats

作　　者：黄茹润 杨娇 刘姗 母育成 赖泳 HUANG Rurun;YANG Jiao;LIU Shan;MU Yucheng;LAI Long(Department of Pharmacology,College of Pharmacy,Dali University,Dali 671000,China)

机构地区：[1]大理大学药学院药理学教研室,云南大理671000

出　　处：《中国民族民间医药》2021年第17期30-37,共8页Chinese Journal of Ethnomedicine and Ethnopharmacy

基　　金：国家自然科学基金资助项目(81360511)。

摘　　要：目的:评价参松养心胶囊、芪苈强心胶囊和通脉养心丸3种抗心血管疾病的中成药对大鼠肝微粒体CYP450酶4种亚型CYP1A2、CYP2C11、CYP2D1和CYP3A1的体外活性影响。方法:选取15.04μmol·L^(-1)咖啡因、4.98μmol·L^(-1)奥美拉唑、7.81μmol·L^(-1)美托洛尔和6μmol·L^(-1)咪达唑仑分别为CYP1A2、CYP2C11、CYP2D1和CYP3A1特异性探针底物,三种抗心血管疾病的中成药分别与4种CYP450酶亚型的混合探针底物在大鼠肝微粒体中共孵育,HPLC测定大鼠肝微粒体孵育体系中探针底物剩余量,求出相应酶活性抑制百分数并计算IC_(50)值。结果:与空白组比较,随着三药浓度增高各亚酶活性呈降低趋势(P<0.05);三药对大鼠肝微粒体CYP1A2、CYP2C11、CYP2D1、CYP3A1的IC_(50)值分别为:参松养心胶囊1.896、31.97、12.37、1.357μmol·L^(-1);芪苈强心胶囊>100、1.513、35.2、6.669μmol·L^(-1);通脉养心丸>100、33.970、0.566、14.380μmol·L^(-1)。结论:参松养心胶囊对CYP1A2、CYP3A1有中度抑制作用,芪苈强心胶囊对CYP2C11、CYP3A1有中度抑制作用,通脉养心丸对CYP2D1有强抑制作用,其余作用不明显。Objectives To evaluate the effects of Shensong Yangxin capsule,Qili Qiangxin capsule and Tongmai Yangxin Pill on the in vitro activities of four subtypes of liver microsomal CYP450 enzyme CYP1A2,CYP2C11,CYP2D1 and CYP3A1 in rats.Methods 15.04μmol·L^(-1) Caffeine,4.98μmol·L^(-1) omeprazole,7.81μmol·L^(-1) metoprolol and 6μmol·L^(-1) midazolam were selected as CYP1A2,CYP2C11,CYP2D1 and CYP3A1 specific probe substrates,respectively.The residual probe substrates in rat liver microsome incubation system were determined by HPLC,the corresponding enzyme activity percentage was calculated and IC_(50) value was calculated,and then the effects of the three drugs on the activity of rat liver microsomal subenzymes in vitro were evaluated.Results The results showed that the IC_(50) values of Shensong yangxin capsules on rat liver microsomes CYP1A2,CYP2C11,CYP2D1 and CYP3A1 were 1.896,12.37,31.97 and 1.357μmol·L^(-1).The IC_(50) values of Qili Qiangxin capsules on rat liver microsomes CYP2C11,CYP3A1,and CYP2D1 were 1.513,6.669,and 35.2μmol·L^(-1),respectively,and IC_(50) values of CYP1A2 were greater than 100μmol·L^(-1).The IC_(50) values of Tongmai Yangxin pill for CYP2C11,CYP2D1,and CYP3A1 were 33.970,0.566,and 14.380μmol·L^(-1),respectively,and IC_(50) values for CYP1A2 were greater than 100μmol·L^(-1).Conclusion Shensong Yangxin capsule had moderate inhibitory effect on CYP1A2 and CYP3A1,but no obvious inhibitory effect on CYP2C11 and CYP2D1,Qili Qiangxin capsule had moderate inhibitory effect on CYP2C11 and CYP3A1,but had no obvious effect on CYP1A2 and CYP2D1,Tongmai Yangxin Pill had strong inhibitory effect on CYP2D1 and had no obvious effect on CYP1A2,CYP2C11 and CYP3A1.

关 键 词：大鼠肝微粒体 参松养心胶囊 芪苈强心胶囊 通脉养心丸 CYP450酶 

分 类 号：R965[医药卫生—药理学]