尿素通道作为新型利尿药靶点的研究进展

Research prgoress in urea transporters as a novel diuretic target

经典利尿药通过排钠排水利尿,会引起机体电解质平衡紊乱等副作用。尿素通道敲除小鼠表现尿浓缩能力降低,提示尿素通道可作为利尿药靶点,其特异性抑制剂可研发成为新型利尿药。本文拟重点介绍尿素通道作为利尿药靶点的研究基础、尿素通道抑制剂的筛选和评价方法及目前已被发现的小分子尿素通道抑制剂。以尿素通道为靶点的新型利尿药适用于治疗充血性心力衰竭、肝硬化腹水和肾病综合征等稀释性低钠血症。

Classical diuretics,which increase urine outputs by excreting sodium and water,may cause electrolyte imbalance and other side effects.The urea transporter knockout mouse models have showed the reduced ability of mice to concentrate urine,indicating that urea transporters could be regarded as a novel diuretic target,and that urea transporter inhibitors could be developed as novel diuretics.This review summarizes the studies on urea transporters as a diuretic target,the screening and evaluation methods of urea transporter inhibitors and the urea transporter inhibitors discovered.Novel diuretics based on urea transporters as targets are suitable for treating the dilutive hyponatremia caused by congestive heart failure,cirrhosis ascites and nephrotic syndrome.