菟丝子水煎液对大鼠肝微粒体细胞色素P450亚型酶活性的影响  

Effects of dodder on the expressions and activities of cytochrome P450 isoforms in rat liver

作　　者：余辉艳[1] 鲍岩岩[1] 于卫江[1] 武正华[1] 朱大岭[1] 

机构地区：[1]哈尔滨医科大学药学院黑龙江省生物医药工程重点实验室哈尔滨医科大学药物与内源性物质代谢省高校重点实验室,黑龙江哈尔滨150081

出　　处：《哈尔滨医科大学学报》2007年第2期105-108,共4页Journal of Harbin Medical University

基　　金：国家863课题资助项目(2002AA2Z3410);黑龙江省自然科学基金重点项目(ZJY03-8)

摘　　要：目的观察菟丝子对大鼠肝细胞色素P450酶系统中CYP1A2,2D6以及3A4 3种亚型活性的影响。方法对照组和实验组大鼠分别经口给予生理盐水和菟丝子水煎液2周,差速离心分离肝微粒体,HPLC法分别测定大鼠肝微粒体中CYP1A2,2D6以及3A4探针药物的代谢率;通过Western blot测定大鼠肝微粒体中CYP1A2,2D6以及3A4蛋白的相对含量。结果①实验组探针药物非那西丁代谢率高于对照组(P<0.05),Western blot分析显示实验组CYP1A2蛋白表达略高于对照组;②实验组探针药物右美沙芬的代谢率明显高于对照组(P<0.05),CYP2D6蛋白表达亦明显高于对照组;③两组间探针药物咪哒唑仑代谢率及CYP3A4蛋白表达无明显差异。结论中药菟丝子水煎液可诱导大鼠肝微粒体中的CYP2D6和CYP1A2,而对CYP3A4无影响。Objective To investigate the influence of dodder on the activities of cytochrome P450（CYP450） system：CYP1A2,CYP2D6,and CYP3A4 in rat liver microsome. Methods Rats were given sodium chloride and dodder decoctum by intragastric administration for two weeks followed by high-performance liquid chromatography （HPLC） to measure metabolism of CYP1A2, CYP2D6, and CYP3A4 in rat liver microsomal reconstituted system respectively. Western blot was used to determine the effects of dodder on the protein expressions of CYP1A2, CYP2D6, and CYP3A4. Results ①The metabolic rate of phenacetin in treated group was higher than that in control group（ P 〈 0.05）;The protein expression of CYP1A2 was also higher than that in control.②The metabolic rate of dextromethorphan in treated group was obviously higher than that in control group（ P 〈 0.05） ;The protein expression of CYP2D6 in treated group was higher than that in control.③The metabolic rate of midazolam and the protein expression of CYP3A4 showed no difference between treated and control groups. Conclusion Traditional Chinese drug dodder decoctum could induce the expressions and activities of CYP2D6 and CYP1A2 in rat liver microsome,but have no effect on that of CYP3A4.

关 键 词：中药菟丝子 细胞色素P450 肝微粒体 蛋白表达 

分 类 号：R927.2[医药卫生—药学]