目的 研究淫羊藿苷元對臨床重要轉(zhuǎn)運體OAT1、OAT3、OATP1B1、OATP1B3、OCT1、OCT2、BCRP、BSEP和P-gp轉(zhuǎn)運蛋白的抑制作用。方法 應(yīng)用過表達各轉(zhuǎn)運體的細(xì)胞株，檢測淫羊藿苷元（0、0.03、0.10、0.30、1.00、3.00、10.00 μmol/L）對hOAT1介導(dǎo)的放射性同位素標(biāo)記底物¹⁴C-對氨基馬尿酸（¹⁴C-PAH）、hOAT3介導(dǎo)的³H-硫酸雌酮銨（³H-ES）、hOATP1B1介導(dǎo)的³H-ES、hOATP1B3介導(dǎo)的³H-雌二醇葡糖苷酸（³H-EG）、hOCT1介導(dǎo)的¹⁴C-溴化四乙胺（¹⁴C-TEA）、hOCT2介導(dǎo)的¹⁴C-TEA、hBCRP介導(dǎo)的³H-ES、MDR1介導(dǎo)的³H-地高辛（³H-Digoxin）、以及hBSEP介導(dǎo)的³H-牛黃膽酸鹽（³H-TCA）轉(zhuǎn)運活性的影響，計算淫羊藿苷元對不同轉(zhuǎn)運蛋白的抑制作用的半數(shù)抑制濃度（IC₅₀）。結(jié)果 與對照組比較，淫羊藿苷元0.3～10 μmol/L濃度對OAT3轉(zhuǎn)運活性發(fā)揮顯著抑制作用（P<0.05），0.1～10 μmol/L對P-gp有顯著抑制作用；1～10 μmol/L濃度對OATP1B3和BCRP轉(zhuǎn)運活性有顯著抑制作用（P<0.05）；3～10 μmol/L濃度對和OATP1B1轉(zhuǎn)運活性有顯著抑制作用（P<0.05）；對OAT3和BCRP轉(zhuǎn)運活性的IC₅₀分別為4.97和8.15 μmol/L；對OAT1B1、OATP1B3、OCT2和P-gp的IC₅₀均大于10 μmol/L，對OAT1、OCT1和BSEP轉(zhuǎn)運活性無明顯影響。結(jié)論 淫羊藿苷元對藥物轉(zhuǎn)運體OAT3和BCRP的抑制作用相對較強，對OAT1B1、OATP1B3、OCT2和P-gp也具有一定的抑制作用，對OAT1、OCT1和BSEP無顯著抑制作用。

Objective To research the inhibition of anhydroicaritin to the important clinical transporters including OAT1, OAT3, OATP1B1, OATP1B3, OCT1, OCT2, BCRP, BSEP, and P-gp. Method The transgenic cell lines overexpressing OAT1, OAT3, OATP1B1, OATP1B3, OCT1, OCT2, BCRP, BSEP, and P-gp were constructed, and the inhibition of anhydroicaritin (0, 0.03, 0.10, 0.30, 1.00, 3.00, and 10.00 μmol/L) on the different transporters were evaluated by the effects of anhydroicaritin on transport activity of the radiolabeled substrates of ¹⁴C-PAH, ³H-ES, ³H-ES, ³H-EG, ¹⁴C-TEA, ¹⁴C-TEA, ³H-ES, ³H-Digoxin, ³H-TCA mediated by hOAT1, hOAT3, OATP1B, hOATP1B3, hOCT1, hOCT2, hBCRP, MDR1,and hBSEP, respectively. The half maximal inhibitory concentration (IC₅₀) of anhydroicartin to every transporters were calculated by the software Prism 5.0. Result Compared with control group, anhydroicaritin of 0.3 - 10 mol/L concentration had significant inhibitory effects on the transport activity of OAT3, BCRP, and OATP1B3 (P<0.05), and concentration of 0.1~10 and 1~10 μmol/L significantly inhibited the P-gp and OATP1B1 transport activity (P<0.05). The IC₅₀ of anhydroicaritin to OAT3 and BCRP transport activity was 4.97 and 8.15 mol/L, respectively, and IC₅₀ of OAT1B1, OATP1B3, OCT2, and P-gp were more than 10 μmol/L, and with no obvious effects on the transport activity of OAT1, OCT1, and BSEP. Conclusion Anhydroicaritin showed strong inhibition to OAT3 and BCRP, and showed certain inhibition to OATP1B1, OATP1B3, OCT2, and P-gp inordinately, but no inhibition to OAT1, OCT1, and BSEP.

國家自然科學(xué)基金重點項目（81430096）；天津市科技支撐重點項目（17YFZCSY01170）；國家青年自然科學(xué)基金（81503154）