摘要
目的研究甘草次酸18位差向异构体即18α-甘草次酸、18β-甘草次酸对Caco-2细胞上P-糖蛋白功能和表达的影响。方法建立Caco-2细胞模型,采用罗丹明-123摄取法评价P-糖蛋白的功能;使用荧光定量PCR检测MDR1 mRNA;Westernblot分析Caco-2细胞膜上P-糖蛋白的表达。结果中、高浓度(1,10μmol.L-1)的18α-甘草次酸和高浓度(10μmol.L-1)的18β-甘草次酸使细胞内罗丹明-123摄取减少。高浓度(10μmol.L-1)的18α-甘草次酸在转录水平上调MDR1 mRNA的表达;实验浓度的18β-甘草次酸未影响MDR1 mRNA的表达;高浓度(10μmol.L-1)18α-甘草次酸对P-糖蛋白有诱导作用,实验浓度的18β-甘草次酸没有影响P-糖蛋白表达。结论 18α-甘草次酸对P-糖蛋白功能和表达的影响均表现为诱导作用,而18β-甘草次酸只对P-糖蛋白功能表现出一定的诱导作用。
OBJECTIVE The aim of our work wasto study the effects of C-18 epimers of glycyrrhetinic acid, 18α-glycyrrbetinie acid （α-GA） and 18/3-glycyrrhetinic acid （β-GA） on the function and expression of P-gp in Caco-2 cell monolayers. METHODS Caco-2 cells were cultured, the effects of P-gp tunction were analyzed by means of rhodamine accumulation test, real-time PCR was used to measure the expression of MDRi mRNA and wesfern blot was used to analysis P-gp expression in Caco-2 cell. RESULTS In the rhodamine accumulation test, middle and high concentrations （1 and 10 μmol·L^-1） α-GA and high concentration （ 10 μmol·L^-1 ） β-GA decreased the cellular rhodamine concentration. At high concentrations （ 10μmol·L^-1）, α-GA up-regulated the expres- sion of MDR1 mRNA while 19-GA has no effect on the expression of MDR1 mRNA at three test concentrations, α-GA up-regulated the expression of P-gp protein at high concentrations （10 μmol·L^-1） while ,8-GA has no effect on the expression of P-gp protein at three test concentrations. CONCLUSION Our findings provide experimental evidence that α-GA up-regulated both function and expression of P-gp while β-GA only up-regulate the function of P-gp.
出处
《中国药学杂志》
CAS
CSCD
北大核心
2012年第1期8-12,共5页
Chinese Pharmaceutical Journal
基金
国家自然科学基金项目子课题(No.30873114)
湖南省自然科学基金重点项目(No.11JJ2052)
湖南省中医药科研计划项目(No.2008086)
