阿司匹林合用琥乙红霉素对大鼠肝细胞色素P450同工酶和mdr1的影响  

Effects of Coadministration of Aspirin with Erythromycin Ethylsuccinate on Liver Microsomal Cytochrome P450 Isoenzyme and mdr l in Rats

作　　者：邹文[1] 周文[2] 欧扬[2] 

机构地区：[1]山东大学药学院,山东济南250012 [2]山东大学齐鲁医院药剂科,山东济南250012

出　　处：《食品与药品》2008年第4期8-12,共5页Food and Drug

基　　金：山东省卫生厅科研基金资助课题(2005HZ044)

摘　　要：目的以大鼠作为实验动物,形成疾病模型,研究阿司匹林合用琥乙红霉素对大鼠肝脏细胞色素P450同工酶和多药耐药基因的影响。方法用分光光度法测定大鼠肝微粒体红霉素N-脱甲基酶(ERD)、氨基比林N-脱甲基酶(ADM)的活性,用逆转录聚合酶链反应(RT-PCR)技术测定大鼠肝脏CYP3A1、CYP1A2、CYP2E1、mdrla和mdrlb基因的水平。结果大鼠连续灌胃给药7d后,与空白组大鼠比较,琥乙红霉素组ERD和ADM活性均明显受抑制(P<0.05),阿司匹林组ERD和ADM活性均不同程度提高,琥乙红霉素与阿司匹林合用组对ERD、ADM活性均表现抑制作用,且对大鼠肝脏CYP3A1、CYP2E1、mdr la、mdr lb基因表达量减少。各组的CYP1A2基因未能检出。结论琥乙红霉素抑制ERD、ADM活性及CYP3A1基因的表达,阿司匹林可对抗琥乙红霉素对肝药酶的抑制作用,两者存在基于肝药酶的相互作用,合用的结果可能导致琥乙红霉素对肝药酶抑制作用减弱。Objective To study the effects of coadministration of aspirin with erythromycin ethylsuccinate on liver microsomal cytochrome P450 isoenzyme and multidrug resistance gene （mdrl） in rats. Methods The activities of liver microsomal erythromycin N-demethylase （ERD）and aminopyrine N-demethylase （ADM） were measured by spectrophotometry. The levels of mRNA expressions of CYP3A1, CYP1A2, CYP2E1, mdrla and mdrlb in hepatic microsome were determined with RT-PCR method. Results After administration for 7 days, the activities of ERD and ADM were markedly inhibited by erythromycin ethylsuccinate（P 〈 0.05）, while the activities were enhanced in different extent by aspirin; the activities of ERD and ADM, mRNA expressions of CYP3A1, CYP2E1, mdrla and mdrlb were all inhibited by the coadministration of erythromycin ethylsuccinate and aspirin. The CYP1A2 gene was not detected in all groups. Conclusion Erythromycin ethylsuccinate can inhibit the activities of ERD and ADM and decrease the expression of CYP3A, while aspirin has an opposite effect against erythromycin ethylsuccinate. The coadministration of aspirin with erythromycin ethylsuccinate may reduce the inhibitory effect of erythromycin ethylsuccinate on liver CYP450.

关 键 词：琥乙红霉素 阿司匹林 细胞色素P450 多药耐药基因 药物相互作用 

分 类 号：R969.2[医药卫生—药理学]