目的 研究淫羊藿苷元對(duì)臨床重要轉(zhuǎn)運(yùn)體OAT1、OAT3、OATP1B1、OATP1B3、OCT1、OCT2、BCRP、BSEP和P-gp轉(zhuǎn)運(yùn)蛋白的抑制作用。方法 應(yīng)用過(guò)表達(dá)各轉(zhuǎn)運(yùn)體的細(xì)胞株，檢測(cè)淫羊藿苷元（0、0.03、0.10、0.30、1.00、3.00、10.00 μmol/L）對(duì)hOAT1介導(dǎo)的放射性同位素標(biāo)記底物¹⁴C-對(duì)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(yùn)活性的影響，計(jì)算淫羊藿苷元對(duì)不同轉(zhuǎn)運(yùn)蛋白的抑制作用的半數(shù)抑制濃度（IC₅₀）。結(jié)果 與對(duì)照組比較，淫羊藿苷元0.3～10 μmol/L濃度對(duì)OAT3轉(zhuǎn)運(yùn)活性發(fā)揮顯著抑制作用（P<0.05），0.1～10 μmol/L對(duì)P-gp有顯著抑制作用；1～10 μmol/L濃度對(duì)OATP1B3和BCRP轉(zhuǎn)運(yùn)活性有顯著抑制作用（P<0.05）；3～10 μmol/L濃度對(duì)和OATP1B1轉(zhuǎn)運(yùn)活性有顯著抑制作用（P<0.05）；對(duì)OAT3和BCRP轉(zhuǎn)運(yùn)活性的IC₅₀分別為4.97和8.15 μmol/L；對(duì)OAT1B1、OATP1B3、OCT2和P-gp的IC₅₀均大于10 μmol/L，對(duì)OAT1、OCT1和BSEP轉(zhuǎn)運(yùn)活性無(wú)明顯影響。結(jié)論 淫羊藿苷元對(duì)藥物轉(zhuǎn)運(yùn)體OAT3和BCRP的抑制作用相對(duì)較強(qiáng)，對(duì)OAT1B1、OATP1B3、OCT2和P-gp也具有一定的抑制作用，對(duì)OAT1、OCT1和BSEP無(wú)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(guó)家自然科學(xué)基金重點(diǎn)項(xiàng)目（81430096）；天津市科技支撐重點(diǎn)項(xiàng)目（17YFZCSY01170）；國(guó)家青年自然科學(xué)基金（81503154）