探针底物法评价柚皮苷对大鼠肝脏CYP3A1/2酶代谢活性的影响  

Estimating the influences of orally administrated naringin on the activity of hepatic cytochrome P450 3A1/2 enzyme in rats using a probe substrate method

作　　者：程可羚 吴灏 白杨[1] 樊威洋 苏薇薇[1] 李沛波[1] CHENG Keling;WU Hao;BAI Yang;FAN Weiyang;SU Weiwei;LI Peibo(School of Life Sciences,Sun Yat-sen University,Guangzhou 510275,China)

机构地区：[1]中山大学生命科学学院

出　　处：《药学研究》2019年第9期503-509,共7页Journal of Pharmaceutical Research

基　　金：国家自然科学基金面上项目(No.31571830)

摘　　要：目的采用体内探针底物法评价柚皮苷连续灌胃给药7 d对大鼠肝脏CYP3A1/2酶代谢活性的影响。方法选择咪达唑仑作为CYP3A1/2的特异性探针底物;将大鼠随机分成对照组和4个柚皮苷给药组,其中对照组灌胃给予等体积超纯水,柚皮苷4个剂量组分别按50、125、250和500 mg·kg^-1剂量灌胃给药连续7 d;给药完成后,尾静脉注射咪达唑仑溶液,于不同时间点采集血样,采用高效液相串联质谱法测定大鼠血浆中咪达唑仑的浓度,利用DAS2.0软件计算咪达唑仑的药动学参数AUC0~t、AUC0~∞、MRT0~t、MRT0~∞、t1/2、V、Cl和C max,以评价柚皮苷对大鼠肝脏CYP3A1/2酶代谢活性的影响。结果与对照组比较,柚皮苷四个剂量组中的咪达唑仑主要药代动力学参数AUC0~t、AUC0~∞、MRT0~t、MRT0~∞、t1/2、V、Cl和C max均无显著差异(P>0.05)。结论大鼠经连续7 d灌胃给予柚皮苷(50~500 mg·kg^-1)后,肝脏CYP3A1/2酶代谢活性未受到显著影响。Objective To evaluate the effect of orally administrated naringin on the activity of hepatic cytochrome P450 3A1/2(CYP3A1/2)enzyme in rats.Methods Midazolam was used as the probe substrate of CYP3A1/2 enzyme in rats.Male SD rats were randomly divided into five groups,including four naringin-treated groups at different doses and control group.The rats in naringin-treated groups were orally administrated with naringin at daily dose of 50,125,250,and 500 mg·kg^-1 for seven days,respectively.The rats in blank control group were given with the same volume normal saline.Midazolam was intravenously administered to rats after giving with naringin,and the blood samples were subsequently collected.A HPLC-MS/MS method was established to determine the concentrations of midazolam quantitively.The pharmacokinetic parameters,including AUC0~t,AUC0~∞,MRT0~t,MRT0~∞,t1/2,V,Cl,and C max were calculated by DAS2.0 software.Results The pharmacokinetic parameters of midazolam in four naringin-treated groups showed no significant difference compared with blank control group(P>0.05).Conclusion Oral administration of naringin at daily dose of 50,125,250,and 500 mg·kg^-1 for seven days did not influence the activity of hepatic CYP3A1/2 enzyme in rats.

关 键 词：柚皮苷 CYP3A1/2 探针底物法 高效液相串联质谱 大鼠 

分 类 号：R969.1[医药卫生—药理学]