肝内胆汁淤积机制的新假说  

New Hypothesis for Intrahepatic Cholestasis

作　　者：于凤爽 范永刚[1] 武民君 李丽华[1] 

机构地区：[1]辽宁医学院基础学院细胞生物教研室,辽宁锦州121001

出　　处：《辽宁医学院学报》2015年第1期90-91,I0006,共3页Journal of Liaoning Medical University (LNMU) Bimonthly

基　　金：国家自然科学基金项目;编号:81200262

摘　　要：胆汁淤积(Cholestasis)是肝脏疾病的一种常见并发症,病理机制尚不清楚。研究表明,胆汁流障碍是导致胆汁淤积的重要因素。胆汁的形成主要依赖于肝细胞内胆盐的分泌,是在胆汁中水份转运的主要驱动力。肝细胞胆小管膜是胆汁分泌的限速步骤。水通道蛋白-8(Aquaporin-8,AQP8)高表达于肝细胞胆小管膜上,跨膜转运水分子进入胆小管。研究表明AQP8在胆汁淤积的小鼠模型中表达下降;我们利用AQP8敲除小鼠发现,AQP8敲除明显减少了胆汁分泌量,胆汁中胆盐显著增加。因此,我们设想AQP8敲除可能通过提高胆盐输出泵的分泌活性增加胆盐浓度,进而损伤胆小管膜,导致胆小管形成减少,最终导致肝内胆汁淤积。AQP8的激动剂或内源性AQP8表达的再激活将是一个治疗肝内胆汁淤积的新策略。Cholestasis is a common complication in liver disease,whose pathological mechanism is still unclear. Recent studies showed that impaired bile flow might mostly result in cholestasis. Bile formation is mainly dependent on the bile salts in hepatocyte,which is the main driving force for water transporting in bile. Canalicular membrane of hepatocytes is a key rate- limiting step for bile secretion. Aquaporin- 8（ AQP8）,is highly expressed on canalicular membrane of hepatocytes,so that the water molecules that are transported through transmembrane enter the canilicular. Some previous studies showed that the expression of AQP8 in experimental models of cholestasis in rats was reduced; it showed by utilizing AQP8 knockout mice that the bile volume was remarkably reduced and the bile salts in bile were greatly increased through AQP8 knockout. Thus,our hypothesis is that AQP8 knockout may possibly improve the secretory activity of bile salt output pump and increase the concentration of bile salts,further damage the canalicular membrane to cause reduction of bile formation,and finally cause intrahepatic cholestasis. According to this hypothesis,activator of AQP8 or reactivation of the expression of endogenetic AQP8 might be a new way to treat intrahepatic Cholestasis.

关 键 词：胆汁淤积 水通道蛋白8(AQP8) 转运蛋白(Bsep) 胆小管 胆汁 

分 类 号：R575[医药卫生—消化系统]