药物转运体对于促进扩散及主动转运药物的吸收具有重要作用,研究其在缺氧时的变化将为提高药物在小肠的吸收提供重要依据。本实验研究了缺氧72 h后P-gp m RNA水平及蛋白水平的变化,并考察了P-gp变化后对其特异性底物(左氧氟沙星)在小肠吸收的影响。结果显示,缺氧后小肠组织中P-gp m RNA与蛋白的相对表达水平分别下调了50.80%和71.30%(P〈0.05);缺氧组30-60、60-90、90-120和120-150 min各时间段的P_(eff)分别增加了56.16%、226.00%、77.74%和141.00%(P〈0.05)。这一结果说明缺氧会导致小肠中P-gp的表达下调,使左氧氟沙星的外排减少,增加其在肠道的吸收。
The drug transporter play a key role in the absorption of drugs. Investigation of the changes of drug transporters in response to hypoxia will provide insight into the mechanism of drug absorption. In this study we investigated the mRNA and protein expression of the transporter P-gp after acute hypoxia, and evaluated the effects of P-gp changes on absorption of levofloxacin in the intestine. The relative expression of mRNA and protein were reduced by 50.80% and 71.30% (P〈 0.05). In the single-pass intestinal perfusion model, the intestinal wall permeability was increased by 56.16%, 226.00%, 77.74% and 141.00% in the time intervals at 30-60 min, 60-90 min, 90-120 min and 120-150 min although P-gp expression was decreased (P〈0.05). These results suggest that hypoxia may decrease the expression of P-gp in the intestine to reduce the excretion of levofloxacin and increase the absorption.