目的 研究小檗堿對人有機(jī)陽離子轉(zhuǎn)運(yùn)蛋白（OCTs）—OCT1、OCT2、OCT3、OCTN1和OCTN2的抑制作用。方法 應(yīng)用由轉(zhuǎn)染試劑Lipo 3 000介導(dǎo)的動物細(xì)胞轉(zhuǎn)基因方法、經(jīng)篩選得到各藥物轉(zhuǎn)運(yùn)體過表達(dá)細(xì)胞株S2-OCT1、S2-OCT2、S2-OCT3、S2-OCTN1和S2-OCTN2；通過檢測OCTs介導(dǎo)的放射性探針底物的跨膜轉(zhuǎn)運(yùn)，建立OCTs體外評價(jià)模型；以野生型（WT）細(xì)胞為對照組，應(yīng)用各轉(zhuǎn)運(yùn)體抑制劑驗(yàn)證其活性；應(yīng)用上述方法觀察小檗堿對各轉(zhuǎn)運(yùn)體的抑制作用，并計(jì)算小檗堿對各藥物轉(zhuǎn)運(yùn)體活性的半數(shù)抑制濃度（IC₅₀）。結(jié)果 各轉(zhuǎn)運(yùn)體細(xì)胞組與各自WT細(xì)胞株比較，轉(zhuǎn)運(yùn)活性均提高了5倍多，加入抑制劑后，轉(zhuǎn)運(yùn)活性均明顯下降；小檗堿對OCT1、OCT2、OCT3和OCTN1抑制作用較強(qiáng)，對OCTN2的抑制作用相對較弱，IC₅₀分別為7.63、6.80、2.25、4.66和210.34 μmol/L。結(jié)論 小檗堿對這5種有機(jī)陽離子轉(zhuǎn)運(yùn)體均有抑制作用，其中對OCT1、OCT2、OCT3、OCTN1的抑制作用較強(qiáng)，發(fā)生由其介導(dǎo)的DDI的可能性較大，對OCTN2的抑制作用相對較弱。

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.

國家自然科學(xué)基金重點(diǎn)項(xiàng)目（81430096）