苦瓜水提物对小鼠肝微粒体CYP3A及肠道P-糖蛋白的影响  

Regulative Effect of Aqueous Extract from Fructus Momordicae Charantiae on Mice Liver Microsomal CYP3A and Intestinal P-glycoprotein

作　　者：李相玲[1] 奇锦峰[2] 周联[1] 林梅[2] 王永辉[2] 韩坚[2] 

机构地区：[1]广州中医药大学临床药理研究所,广州510405 [2]广州中医药大学中药学院,广州510006

出　　处：《中药新药与临床药理》2010年第6期618-621,共4页Traditional Chinese Drug Research and Clinical Pharmacology

摘　　要：目的研究苦瓜水提物对小鼠肝脏细胞色素氧化酶P450(CYP450)中CYP3A及肠道药物转运体P-糖蛋白(P-gp)的影响,以推测苦瓜水提物对人CYP3A及P-gp的影响。方法小鼠经口投与苦瓜水提物粉末低、高剂量(10,50 mg/kg,2次/d)1周,取肝脏以差速离心法分离肝微粒体,用Bradford法定量蛋白;以红霉素法和氨基比林法定量CYP3A的活性。小鼠经口投与苦瓜水提物粉末低、中、高剂量(10,50,250 mg/kg)1次,以扑热息痛(25 mg/kg)为测定P-gp活性的探针药,通过分光光度法测定血清中扑热息痛浓度来推测苦瓜水提物对肠道P-gp的影响。结果与蒸馏水对照组相比,苦瓜水提物高剂量对小鼠肝CYP3A具有明显的抑制作用(P<0.05)。苦瓜水提物250 mg/kg灌胃后30 min,可使血清中扑热息痛的浓度明显升高(P<0.05),说明其显著抑制了肠道P-gp。结论苦瓜水提物在大剂量服用时可抑制小鼠肝脏CYP3A的活性及肠道P-gp的活性。Objective To study the influence of aqueous extract of Fructus Momordicae Charantiae（FMC） on the CYP3A in mice liver microsomal cytochrome oxidase P450 and on intestinal transporter P-glycoprotein（P-gp）,thus to infer its possible effect on human CYP3A and P-gp.Methods（1） After intragastric administration of low and high dosages of FMC aqueous extract powder（10,50 mg/kg,bid） for one week,liver microsomes were separated by ultracentrifugation,and the protein concentrations were quantified by Bradford method.The CYP3A activities were tested by using erythromycin and aminopyrine as substrates.（2） Mice were orally given with low,middle and high dosages of FMC aqueous extract powder（10,50,250 mg/kg,qd）.Paracetamol（25 mg/kg）was used as the probe drug for the observation of impact of FMC water extract on intestinal P-gp by determining the serum paracetamol concentrationton with spectrophotometry.Results（1） Compared with the blank control group,high-dose of FMC water extract significantly inhibited mice liver microsomal CYP3A（P〈0.05）.（2）FMC water extract in the dosage of 250 mg/kg could significantly enhance the serum concentration of paracetamol 30min after medication（P〈0.05 compared with the control group）,indicating that the intestinal P-gp level was inhibited.Conclusion Large-dosage FMC water extract can inhibit the activity of hepatic microsomal CYP3A and intestinal P-gp activity.

关 键 词：苦瓜水提物 CYP3A 红霉素 氨基比林 P-糖蛋白 扑热息痛 

分 类 号：R285.5[医药卫生—中药学]