清肺排毒汤对大鼠肝脏主要药物代谢酶活性和mRNA表达的影响  

Effects of Qingfei Paidu decoction on the activity and mRNA expression of drug metabolizing enzymes in rat liver

作　　者：廖鑫娅 杨文竹 吕季桐 汪金悦 王兴[2] LIAO Xinya;YANG Wenzhu;LüJitong;WANG Jinyue;WANG Xing(School of Life Science and Engineering,Southwest Jiaotong University,Chengdu,Sichuan,610000 P.R.China;College of Medicine,Southwest Jiaotong University,Chengdu,Sichuan,610000 P.R.China)

机构地区：[1]西南交通大学生命科学与工程学院,四川成都610000 [2]西南交通大学医学院,四川成都610000

出　　处：《华西药学杂志》2024年第6期669-674,共6页West China Journal of Pharmaceutical Sciences

基　　金：中央高校基本科研业务费专项资金(2682020XG10,2682022ZTPY025)。

摘　　要：目的研究清肺排毒汤(QPD)对大鼠肝脏主要药物代谢酶活性和mRNA表达的影响。方法大鼠连续灌胃QPD 7 d,末次给药后,尾静脉注射探针药物,采用HPLC测定血样中探针药物的浓度。通过比较各组间探针药物的血浆药动学,分析QPD对细胞色素P450酶(CYP450)活性的影响。采用ELISA分析QPD对大鼠肝脏葡萄糖醛酸转移酶(UGTs)活性的影响。通过实时荧光定量PCR检测CYP450和UGTs mRNA的表达。结果QPD能提高CYP2C9、CYP2C19、CYP2E1酶的活性及mRNA的表达,抑制CYP1A2酶的活性及mRNA的表达,且对UGT1A2、UGT1A3、UGT1A8有诱导作用,对UGT2B7、UGT1A9有抑制作用。结论QPD能选择性地影响大鼠肝脏主要药物代谢酶的活性。OBJECTIVE To study the effects of Qingfei Paidu decoction(QPD)on the activity and mRNA expression of major drug-metabolizing enzymes in rat liver.METHODS After 7 days of continuous intragastric administration of QPD,rats were injected with probe drugs,and the concentrations of probe drugs in plasma were determined by HPLC.The influence of QPD on the activities of cytochrome P450(CYP450)was investigated by comparing plasma pharmacokinetics of probe drugs between control and QPD groups.The effects of QPD on the rat liver UGTs activity were studied through ELISA.The relative expression levels of CYP450 and UGTs mRNA were detected by real-time quantitative PCR(RT-qPCR).RESULTS QPD could significantly induce the expression and activity of CYP2C9,CYP2E1,and CYP2C19,while inhibit the enzyme activity,and mRNA expression of CYP1A2.The result also showed that the activity of UGT1A2,UGT1A3,and UGT1A8 was increased and the activity of UGT2B7,and UGT1A9 was inhibited.CONCLUSION QPD has selective regulations on major drug-metabolizing enzymes in rat liver.

关 键 词：清肺排毒汤 药物代谢酶 细胞色素P450酶 葡萄糖醛酸转移酶 肝脏代谢 大鼠 Cocktail探针法 

分 类 号：R96[医药卫生—药理学]