调控血脑屏障ABC转运体信号转导通路的研究现状

Study status of signaling pathways that regulate ABC transporter activity at the blood-brain-barrier

血脑屏障中的ABC转运体是介导内源性物质、药物和毒物转运的一类外排转运体,主要包括P-糖蛋白(P-gp)、多药耐药相关蛋白(Mrp)以及乳腺癌耐药蛋白(Bcrp)。这类转运体能限制外来异物进入中枢神经系统,使得很多治疗药物难以透过血脑屏障产生治疗作用,阐明这些转运蛋白的转运机制,可为药物的中枢转运提供新的靶点,有助于降低脑部耐药的发生,改善药物治疗的结局。本文主要针对ABC转运体以及涉及的肿瘤坏死因子-α/蛋白激酶C-β/鞘氨醇1磷酸酯受体1(TNF-α/PKCβ/S1PR1)信号通路、血管内皮生长因子信号通路和雌激素受体信号通路进行探讨。

ATP-binding cassette （ ABC ） transporters at blood-brain barrier, such as, P-glycoprotein （ P -gp ） , multidrug -resistance -associated protein （ Mrp ） , and breast cancer related protein （ Bcrp ） , can limit central nervous system （ CNS ） uptake of foreign chemicals, drugs and toxicant.ABC transporters are neuroprotective, but they also distinguish poorly between neurotoxicants and therapeutic drugs.So they are major obstacles to CNS pharmacotherapy.Clarifying the mechanisms of these transporters can provide new targets for drugs to get through the blood-brain barrier, which helps to reduce the occurrence of drug re-sistance and improve the effect of treatment.The present review is fo-cused on new findings about ABC transporters and three main signal path-ways, whose are TNF-α/PKCβ/S1PR1 signaling, vascular endothelial growth factor signaling and estrogen signaling.