槲皮素对鸡P-糖蛋白转运功能的影响

Effect of quercetin on the transport function of chicken P-glycoprotein

为了探讨槲皮素对鸡小肠P-糖蛋白(P-gp)转运功能的影响,选用槲皮素(10和50μmol/L)处理MDCK-ch Abcb1细胞系后分别进行美托洛尔和伊维菌素的双向转运试验;采用不同剂量的槲皮素(15和60 mg/kg)连续灌流5或10 d后进行美托洛尔的原位灌流试验,用60 mg/kg槲皮素处理试验组鸡10 d后进行伊维菌素的灌流试验。结果显示:10和50μmol/L槲皮素均能显著(P<0. 05)增强MDCK-chAbcb1细胞对美托洛尔的外排作用,外排率可从1. 89分别增至2. 95和2. 36,但均对MDCK细胞无显著影响(P>0. 05);灌流试验结果显示不同浓度的槲皮素均极显著降低美托洛尔的小肠有效渗透率(Peff)(P<0. 01),尤其低浓度槲皮素的作用更为显著; 60 mg/kg的槲皮素处理组虽能降低P-gp底物伊维菌素的Peff,但与对照组相比,差异不显著(P>0. 05)。结果表明:槲皮素在一定程度上会影响鸡P-gp的外排转运功能,在畜牧生产中使用时应注意考虑药物-饲料间相互作用,避免其对底物药物的体内过程产生影响。该结果可为临床制定合理的用药策略提供理论基础。

To explore whether quercetin affects the function of chicken small intestine P-glycoprotein( P-gp) and thus mediates drug-feed interactions,we combined MDCK cell line overexpressing chicken small intestine P-gp with in situ single-pass intestinal perfusions in chicken jejunum by means of different concentrations of quercetin. The cells used for the bidirectional transport of metoprolol and ivermectin were treated with different concentrations of quercetin at 10 and 50 μmol/L,respectively. The chickens were treated with 15 and 60 mg/kg quercetin for 5 and 10 d,respectively,and with perfusion of metoprolol;and the chickens were treated with 60 mg/kg quercetin for 10 d for ivermectin perfusion. The results showed that 10 and 50 μmol/L quercetin significantly( P<0. 05) enhanced the efflux effect of MDCK-ch Abcb1 cells on metoprolol,and the efflux ratio( ER) increased from 1. 89 to 2. 95 and 2. 36,respectively;but no significant effect was observed on MDCK cells( P>0. 05). The perfusion experiments showed that different concentrations of quercetin,especially the low concentration,significantly reduced the effective intestinal permeability( Peff) of metoprolol( P<0. 01);the Peffof ivermectin was reduced in the group treated with 60 mg/kg of quercetin,but the difference was not significant compared with the control group( P>0. 05). The present study indicated that quercetin had effect on the efflux transport function of chicken P-gp to a certain extent. When using it in livestock production,attention should be paid to the drug-feed interaction to avoid its influence on the substrate drug. This result provided a theoretical reference for the clinical development of a rational drug strategy.