目的 研究小檗碱对人有机阳离子转运蛋白（OCTs）—OCT1、OCT2、OCT3、OCTN1和OCTN2的抑制作用。方法 应用由转染试剂Lipo 3 000介导的动物细胞转基因方法、经筛选得到各药物转运体过表达细胞株S2-OCT1、S2-OCT2、S2-OCT3、S2-OCTN1和S2-OCTN2；通过检测OCTs介导的放射性探针底物的跨膜转运，建立OCTs体外评价模型；以野生型（WT）细胞为对照组，应用各转运体抑制剂验证其活性；应用上述方法观察小檗碱对各转运体的抑制作用，并计算小檗碱对各药物转运体活性的半数抑制浓度（IC₅₀）。结果 各转运体细胞组与各自WT细胞株比较，转运活性均提高了5倍多，加入抑制剂后，转运活性均明显下降；小檗碱对OCT1、OCT2、OCT3和OCTN1抑制作用较强，对OCTN2的抑制作用相对较弱，IC₅₀分别为7.63、6.80、2.25、4.66和210.34 μmol/L。结论 小檗碱对这5种有机阳离子转运体均有抑制作用，其中对OCT1、OCT2、OCT3、OCTN1的抑制作用较强，发生由其介导的DDI的可能性较大，对OCTN2的抑制作用相对较弱。

Objective To study the inhibitory effects of berberine on human organic cation transporter (OCTs) including OCT1, OCT2, OCT3, OCTN1 and OCTN2. Methods Using animal cell transgenic method mediated by transporter Lipo 3000, the drug transporters over expression cell lines S2-OCT1, S2-OCT2, S2-OCT3, S2-OCTN1 and S2-OCTN2 were obtained by selective medium culture. The OCTs evaluation model was established by detecting the trans-membrane transport of radioactive substrate in vitro. Wild type (WT) cells were used as control group, activity of OCTs was verified by adding its inhibitor. The inhibition of berberine on the transporters was investigated in vitro. The IC₅₀ of inhibitory effect of berberine on various drug transporters was also calculated. Results The transport activity of transporter cell lines was increased by more than 5 times compared to the WT cell line respectively, what's more, their transport activity decreased significantly by their corresponding inhibitor. The IC₅₀ of berberine to OCT1, OCT2, OCT3, OCTN1 and OCTN2 were respectively 7.63, 6.80, 2.25, 4.66 and 210.34 μmol/L. Conclusion Berberine significant inhibition to OCT1, OCT2, OCT3, OCTN1 and OCTN2. The inhibition on OCT1, OCT2, OCT3, OCTN1 is stronger compared to OCTN2.

国家自然科学基金重点项目（81430096）