18α-、18β-甘草次酸对他林洛尔在Caco-2细胞上外向转运的影响  

Effect of 18α-glycyrrhetinic acid and 18β-glycyrrhetinic acid on outward transport of talinolol in Caco-2 cell monolayers

作　　者：颜苗[1,2] 方平飞[1,2] 李焕德[1,2] 郑媚 徐萍[1,2] 李兰芳[1,2] 张金娇 

机构地区：[1]中南大学湘雅二医院药学部,湖南长沙410011 [2]中南大学临床药学研究所,湖南长沙410011 [3]防城港市第一人民医院,广西防城港538021 [4]梧州制药股份有限公司,广西梧州543002

出　　处：《中国医院药学杂志》2012年第6期405-409,共5页Chinese Journal of Hospital Pharmacy

基　　金：国家自然科学基金项目(编号:30873114);湖南省自然科学基金重点项目(编号:11JJ2052);湖南省中医药科研计划项目(编号:2008086)

摘　　要：目的:研究甘草次酸18位差向异构体即18α-甘草次酸(α-GA)、18β-甘草次酸(β-GA)对P-糖蛋白(P-gp)底物他林洛尔在Caco-2细胞上外向转运的调控作用。方法:建立Caco-2单层细胞模型,以P-gp底物他林洛尔为探针药物,评价α-GA、β-GA和P-gp抑制剂维拉帕米对他林洛尔在Caco-2细胞上外向转运的影响。HPLC法测定细胞转运液中他林洛尔的浓度,采用Luna C18色谱柱(4.6 mm×250 mm,5μm),流动相乙腈-甲醇-10 mmol·L-1醋酸铵(25∶10∶65,v/v/v),流速1.0mL·min-1,检测波长248 nm。结果:浓度为10μmol·L-1的α-GA、β-GA使他林洛尔TransportB-A增加,他林洛尔BL-AP表观渗透系数(Papp B-A)增大,对他林洛尔外向转运表现出诱导作用;α-GA诱导P-gp外排他林洛尔的能力强于β-GA。结论:α-GA、β-GA能诱导P-gp的外向转运,加速P-gp底物的外排,可能是甘草酸制剂增强肝脏解毒的机制之一。OBJECTIVE To study the effects of C-18 epimers of glycyrrhetinic acid, 18u-glycyrrhetinic acid （a-GA） and 18/3 glycyrrhetinic acid （β GA）, on outward transport of P gp substrate talinolol in Caco-2 cell monolayers. METHODS Appropri ate Caco-2 monolayers were established, talinolol was used as a probe drugs. The efflux of talinolol in Caco 2 monolayers after treated for 72 h by toGA ,β-GA and verapamil was investigated. HPLC was applied to detect the concentration of talinolol in transfer fluids. The analyte was separated on a Luna C18 column （4. 6 mm × 250 mm, 5 bcm） and an isocratic mobile phase of acetonitrile-methanol-water containing ammonium acetate （10 mmol.L-1 ） （25： 10：65, v/v/v） at a flow rate of 1.0 mL.min-1. The detection wavelength was 248 nm. RESULTS 1（1 umol.L-1 a-GA and β-GA increased the Transport DA of talino101 in the incubation for 72 h test. Papp B-A of talinolol was increased after treatment, a-GA and β-GA induced the efflux of talinolol in this test and the inducibility of α-GA was better than that of β-GA. CONCLUSION The results of the transport experiments of P- gp substrates on Caco-2 monolayers indicated that a-GA and β-GA can induce the efflux function of P-gp and accelerate the excretion of P-gp substrates. It may be one of the mechanisms of that glycyrrhizin preparation enhance liver detoxification.

关 键 词：甘草次酸 差向异构体 P-糖蛋白 他林洛尔 外向转运 

分 类 号：R969[医药卫生—药理学]