P-糖蛋白与血脑屏障

P-Glycoprotein and Blood-Brain Barrier

P-糖蛋白是ATP结合盒转运超家族成员之一,在体内许多部位均有表达,与多药耐药性有关。作为一种外排泵,血脑屏障内的P-糖蛋白能排出内源性底物和外源性化学物质以保持脑内环境的稳定,但同时也限制了治疗性药物在脑内的浓度,从而使治疗效果减弱。P-糖蛋白抑制剂可促进药物通过血脑屏障,对提高脑内药物的浓度和中枢神经系统药物的生物利用度具有重要意义。

P-glycoprotein is one of the members in the superfamily of ATP-binding cassette transporters. It is expressed in many sites in vivo, and is correlated with multidrug resistance. Under physiological conditions, as an efflux pump, P-glycoprotein in the blood-brain barrier can eliminate endogenous substrates and xenobiotics to maintain the balance of internal environment. But at the same time, it also limits the concentration of therapeutic drugs in brain, and thus reduces therapeutic efficacy. P-glycoprotein inhibitors can get drugs across the blood-brain barrier. It is of great importance to improve the blood concentration in brain and bioavailability of central nervous system drugs.