目的 系統(tǒng)研究Caco-2細(xì)胞中各藥物轉(zhuǎn)運(yùn)蛋白的mRNA表達(dá)水平及轉(zhuǎn)運(yùn)活力，對(duì)比其與人正常腸道中藥物轉(zhuǎn)運(yùn)蛋白表達(dá)的差異。方法 實(shí)時(shí)熒光定量PCR（qRT-PCR）方法測(cè)定Caco-2細(xì)胞中人腸道相關(guān)轉(zhuǎn)運(yùn)蛋白MDR1、BCRP、MRP2、OATP1A2、OATP2B1和PEPT1的表達(dá)水平；將Caco-2細(xì)胞接種于Transwell板內(nèi)培養(yǎng)21 d并給予不同藥物轉(zhuǎn)運(yùn)蛋白的底物及抑制劑，評(píng)價(jià)Caco-2細(xì)胞中相關(guān)轉(zhuǎn)運(yùn)蛋白的轉(zhuǎn)運(yùn)活性。結(jié)果 qRT-PCR結(jié)果表明，藥物轉(zhuǎn)運(yùn)蛋白MDR1、MRP2、BCRP和OATP2B1在Caco-2細(xì)胞中均有相對(duì)高的表達(dá)，表達(dá)量的順序?yàn)椋篗DR1 > MRP2 > OATP2B1 > BCRP，在正常人腸道表達(dá)量順序?yàn)锽CRP > MDR1 > MRP2 > OATP2B1；轉(zhuǎn)運(yùn)蛋白活力評(píng)價(jià)表明，各藥物轉(zhuǎn)運(yùn)蛋白的活力測(cè)試結(jié)果均為陽(yáng)性，驗(yàn)證了基因的表達(dá)水平結(jié)果。結(jié)論 Caco-2細(xì)胞中表達(dá)正常人體腸道表達(dá)的部分藥物轉(zhuǎn)運(yùn)蛋白（MDR1、MRP2、BCRP和OATP2B1），表達(dá)水平與正常人體腸道中大致相當(dāng)，但也存在一定差異。

Objective To study the mRNA expression and transport activity of drug transporters in Caco-2 cells, and compare the differences of the expression of drug transporters between Caco-2 cells and human normal intestinal. Method Establishing a method for the determination of mRNA expression of drug transporter by qRT-PCR method to determine the expression levels of human intestinal related transport proteins MDR1, BCRP, MRP2, OATP1A2, OATP2B1, and PEPT1 in Caco-2 cells; Caco-2 was then seeded in Transwell plates for 21 days and administered with different drug transporter substrates and inhibitors to assess the transporter activity of the relevant transporter in Caco-2 cells. Results The qRT-PCR results indicated that MDR1, MRP2, BCRP, and OATP2B1 were relatively higher expressed in Caco-2 cells. The relative expression levels of various drug transporters were as follows:MDR1 > MRP2 > OATP2B1 > BCRP, the expression level of intestinal tract in normal subjects was BCRP > MDR1 > MRP2 > OATP2B1. Drug transporter activity assessment showed that all drug transporter activity test results were positive, validating the expression level of the previous drug transporter gene. Conclusions The expression levels of many drug transporters (MDR1, MRP2, BCRP and OATP2B1) originated from normal human intestinal tract expressed in Caco-2 cells were roughly equivalent to those expressed in the normal human intestinal tract, but there were also some differences between them.

國(guó)家自然科學(xué)基金青年科學(xué)基金項(xiàng)目（81503154）；國(guó)家重點(diǎn)研發(fā)計(jì)劃應(yīng)用系統(tǒng)生物學(xué)結(jié)合PK-PD研究烏頭湯藥性配伍理論（2016YFE0121400）