肝脏转运体表达和功能的变化对肝疾病的影响

Effect of altered expression and function of hepatic transporters on liver disease

转运体是药物吸收、分布、代谢和排泄的重要决定因素,在肝脏表达尤为广泛.肝脏转运体可以摄取大多数内源性物质、营养物质和外源性物质进入肝脏,在肝脏内经过一系列的代谢转化,最终将其外排入胆汁并由胆汁排到肝外.越来越多的证据表明肝脏疾病状态下转运体的表达和功能会发生改变,影响药物在体内的处置过程,进而增加药物相互作用的可能性,同时加大了疾病药物治疗的难度.本文从肝脏摄取型和外排型转运体两方面出发,针对肝脏转运体表达和功能的变化对肝疾病的影响作一综述.

Hepatic transporters are extensively expressed in the human body, especially in the liver. They are important determinants for drug absorption, distribution, metabolism and excretion. Most of endogenous substances, nutrients and exogenous substances can be transported into hepatocytes by hepatic uptake transporters. After metabolism, their metabolic products are excreted into bile. All the clinical relevance of hepatic transporters in drug disposition depends on their localization on the membrane of hepatocytes. There has been growing evidence regarding the importance of liver disease status on alterations in hepatic transporter proteins, which can increase the difficulty of drug therapy by influencing the process of drug disposition. This review focuses on uptake and efflux transporter proteins in the liver and summarizes the effect of alterations of hepatic transporter expression and function on liver disease.