Roberts Derek J, Goralski Kerry B
Faculty of Medicine, Dalhousie University, 5849 University Avenue, Halifax, N.S., B3H 4H7, Canada.
Expert Opin Drug Metab Toxicol. 2008 Oct;4(10):1245-64. doi: 10.1517/17425255.4.10.1245.
P-glycoprotein is a blood-brain barrier efflux transporter that limits drug accumulation in the brain.
To review recent in vivo and in vitro investigations that examined the influence of inflammation, infection and related clinical neuroinflammatory disorders on P-glycoprotein expression and activity in the brain.
Critical overview of English-language studies.
RESULTS/CONCLUSIONS: Inflammation and infection produce dynamic changes in P-glycoprotein expression and activity in the blood-brain barrier. In vitro, blood-brain barrier P-glycoprotein activity is downregulated after short-term exposure to inflammatory mediators whereas its activity is upregulated following more prolonged exposure. In vivo studies in both humans and animals have linked CNS inflammation, peripheral inflammation and related clinical neuroinflammatory disorders with alterations in the expression and activity of blood-brain barrier P-glycoprotein. The direction and degree of change in P-glycoprotein activity depends on the in vivo or in vitro model examined, the cell type examined (e.g., endothelial or glial), the inflammatory mediator utilized, the anatomic site in which the inflammatory response was first generated, the time points chosen for observation and the substrates analyzed. Alterations in P-glycoprotein activity affect drug activity in the CNS and seem clinically important.
P-糖蛋白是一种血脑屏障外排转运体，可限制药物在脑内的蓄积。
综述近期有关炎症、感染及相关临床神经炎症性疾病对脑内P-糖蛋白表达及活性影响的体内和体外研究。
对英文研究进行批判性综述。
结果/结论：炎症和感染可导致血脑屏障中P-糖蛋白的表达及活性发生动态变化。在体外，短期暴露于炎症介质后血脑屏障P-糖蛋白活性下调，而长期暴露后其活性上调。人和动物的体内研究均表明，中枢神经系统炎症、外周炎症及相关临床神经炎症性疾病与血脑屏障P-糖蛋白的表达及活性改变有关。P-糖蛋白活性变化的方向和程度取决于所研究的体内或体外模型、所检测的细胞类型（如内皮细胞或神经胶质细胞）、所使用的炎症介质、炎症反应最初发生的解剖部位、选择观察的时间点以及所分析的底物。P-糖蛋白活性的改变会影响药物在中枢神经系统中的活性，且在临床上似乎具有重要意义。
