以维生素A缺乏症为动物模型，用P-糖蛋白(P-GP)和乳腺癌耐药蛋白（BCRP）的底物作为工具药，结合Western Blot 和QT-PCR技术研究在维生素A缺乏的大鼠脑、肝和肾中P-GP和BCRP等转运体功能与表达的改变；并结合组织中信号通路蛋白水平的变化，在体分析引起转运体功能与表达改变的机制；并且对转运体这种改变特性对其底物药物辛伐他汀和格列本脲在维生素A缺乏的大鼠体内处置的影响进行研究。离体细胞水平以原代细胞或细胞株为对象，研究与不同浓度的维生素A和信号通路抑制剂共培养后，转运体功能和表达改变的程度；并于离体水平分析引起转运体功能与表达改变的机制；再用转染P-GP和BCRP基因的细胞株验证上述实验结果。其成果对于了解维生素A缺乏人群体内P-GP和BCRP功能与表达的改变及其机制以及对其底物药物体内处置的影响具有十分重要的意义，并为进一步指导临床合理用药及不良反应控制提供理论依据。

The aim of the subject is to research on the alterations of P-glycoprotein(P-GP) and breast cancer resistance protein（BCRP） function and expression in brain, liver and kidney of hypovitaminosis A rats, using Rho123 /vincristine and prazosin/Cimetidine as substrats and combining with Western Blot and QT-PCR technology. Moreover, the mechanism of the alterations of P-GP and BCRP in tissues will be analyzed in vivo through the changes of organization signaling pathway proteins such as RXR, RAR, ERK, MAPK, PKC and NF-kB. Besides, the distribution changes of their substrate drugs Simvastatin and Glibenclamide will be further investigated. On the cellular level, the changes of P-GP and BCRP function and expression will be validated using primary cells and cell lines co-cultured with different concentrations of vitamin A and signal pathway inhibitors. The results will be further verified by P-GP-MDCK and BCRP-MDCK cells and the mechanism of P-GP and BCRP changes will be also analyzed in vitro. The result of the subject has an extremely significance on understanding the alterations and mechanism of P-GP and BCRP function and expression and the influence on drug distribution in hypovitaminosis A crowd. Moreover, the result may provide important theory basis for guide clinical rational administration and adverse reaction control.