柴胡注射液对大鼠细胞色素P450各亚型活性的影响  

Role of cytochrome P450 on the metabolism of injection bupleuri

作　　者：王晶[1] 余辉艳[1] 郭蕾[1] 刘艳[2] 朱大岭[1] 

机构地区：[1]哈尔滨医科大学药学院 [2]哈尔滨医科大学附属第二医院药学部

出　　处：《中国临床药理学与治疗学》2007年第9期1037-1041,共5页Chinese Journal of Clinical Pharmacology and Therapeutics

基　　金：黑龙江省自然基金(ZJY03-8)

摘　　要：目的:观察柴胡注射液对大鼠细胞色素P450各亚型活性的影响。方法:24只Wistar大鼠,随机分成3组:对照组,柴胡注射液低、高剂量组。3组分别腹腔注射生理盐水、0.36、0.72mL/kg(相当于原药材0.72、1.44g/kg)柴胡注射液诱导两周后,于d15清晨灌胃给予探针药物咖啡因(10mg/kg),6h后处死。用HPLC法观察探针药物代谢率的变化来反映柴胡注射液对大鼠CYP1A2活性的影响;West-ernbloting测定大鼠肝微粒体CYP1A2、3A4、4A1蛋白的相对含量。结果:体内、外探针药物代谢率在各剂量组及对照组间均无统计学差异(P>0.05),CYP1A2在各剂量组中表达亦无统计学差异。CYP3A4在柴胡注射液高剂量组中表达明显增多(P<0.05),CYP4A1在柴胡注射液低、高剂量组表达均明显减少(P<0.05)。结论:柴胡注射液对大鼠CYP1A2亚型没有影响,但在蛋白质水平,可抑制大鼠肝CYP4A1表达。高剂量柴胡注射液可诱导大鼠肝CYP3A4表达。AIM：To identify the effects of injection bupleuri.on activity of CYPs subgroups.METHODS：The activity of CYP1A2 was determined by measuring the ratio of caffeine and its metabolite in whole blood in vivo by HPLC and the ratio of phenacetin and its metabolite in liver microsomes in vitro.The expression of CYP1A2、3A4、4A1 in three groups were examined by Western blotting.RESULTS：There were no significant difference between probes metabolic rates among groups in vivo and in vitro（P〉0.05）.Also there were similar expression of CYP1A2 in rat liver microsomes from control and treated groups.The expression of CYP3A4 increased in the high dose bupleuri.group.the expression of CYP4A1 obviously decreased in bupleuri.groups.CONCLUSION：Injection bupleuri can inhibit CYP4A1 and induce CYP3A4 expression in rat livers.however it does not effect rat CYP1A2 in vivo or in vitro obviously.

关 键 词：细胞色素P450 探针药物 柴胡注射液 肝微粒体 

分 类 号：R965.2[医药卫生—药理学]