肝性脑病是肝损伤主要并发症。我们前期发现肝损伤大鼠血脑屏障（BBB）上P-糖蛋白（P-GP）功能与表达受损，而多药耐药相关蛋白2（MRP2）功能与表达加强。用其特异性底物以及western blot和QT-PCR等研究肝损伤大鼠BBB上P-GP、MRP2和乳腺癌耐药蛋白（BCRP）等ABC转运体功能与表达改变及机制；这种改变对脑内神经类固醇蓄积和苯巴比妥等底物药物在脑内处置影响；高血氨等对大鼠BBB上P-GP、MRP2和BCRP等ABC转运体功能与表达影响。用脑血管内皮细胞研究肝损伤大鼠血清或铵盐等血清异常成分对P-GP、MRP2和BCRP等ABC转运体功能与表达影响、相关的信号通路及其脑内神经类固醇在细胞中转运，其结果进一步用基因沉默和基因转染细胞验证。其成果对于阐明BBB上P-GP、MRP2和BCRP等ABC运体在肝性脑病中作用、临床合理用药和不良反应预测有重要意义。

Hepatic encephalopathy is a main neuropsychiatric complication of both acute and chronic liver failure. Our previous study showed that liver injury induced by thioacetamide impaired function and expression of P-glycoprotein(P-GP), but enhanced function and expression of multidrug resistance-assocaited protein 2(MRP2) at blood brain barrier(BBB) of rats. The aim of the project was to investigate:1)function and expression of ABC(ATP-binding cassette) transporters including P-GP, MRP2 and breast cancer resistance protein(BCRP) in BBB of rats suffered from liver injury using their specific substrates, western blot and QT-PCR; their alteration in ABC trnasporter-dependent manner; effect of the alterations in function and expresssion of the ABC transporters on neurosteroid accumulations and dispostion of substrate drugs in brain of rats suffered from liver injury. In vitro, effect of serum derived from rats suffered from liver injury and their abnormal components such as ammonemia on expression and function of the ABC transporters in rat brain microvessel endothelial cells(rBMECs).At the same time, the signaling proteins involved in the regulation of ABC transporters were also documented. Transport characters of neurosteroids across rBMEC monolayer were also measured to investigate contribituion the ABC transporters to transport of the neurosteroids across BBB.Some results obtained in the cells were further confirmed using gene silence and gene transfection. The results may highlight the roles of ABC transporter alteration at BBB in development of hepatic encephalopathy as well as guidance for drug use and prediction of drug adverse effects in patents suffered liver injury.