Lehmann Guillermo-L, Larocca Maria-C, Soria Leandro-R, Marinelli Raul-A
Instituto de Fisiologia Experimental Facultad de Ciencias Bioquimicas y Farmaceuticas, UNR, Santa Fe, Argentina.
World J Gastroenterol. 2008 Dec 14;14(46):7059-67. doi: 10.3748/wjg.14.7059.
This review focuses on current knowledge on hepatocyte aquaporins (AQPs) and their significance in bile formation and cholestasis. Canalicular bile secretion results from a combined interaction of several solute transporters and AQP water channels that facilitate water flow in response to the osmotic gradients created. During choleresis, hepatocytes rapidly increase their canalicular membrane water permeability by modulating the abundance of AQP8. The question was raised as to whether the opposite process, i.e. a decreased canalicular AQP8 expression would contribute to the development of cholestasis. Studies in several experimental models of cholestasis, such as extrahepatic obstructive cholestasis, estrogen-induced cholestasis, and sepsis-induced cholestasis demonstrated that the protein expression of hepatocyte AQP8 was impaired. In addition, biophysical studies in canalicular plasma membranes revealed decreased water permeability associated with AQP8 protein downregulation. The combined alteration in hepatocyte solute transporters and AQP8 would hamper the efficient coupling of osmotic gradients and canalicular water flow. Thus cholestasis may result from a mutual occurrence of impaired solute transport and decreased water permeability.
本综述聚焦于目前关于肝细胞水通道蛋白（AQPs）的知识及其在胆汁形成和胆汁淤积中的意义。胆小管胆汁分泌是几种溶质转运体和AQP水通道共同相互作用的结果，这些水通道可促进水在因渗透梯度产生时的流动。在胆汁分泌过程中，肝细胞通过调节AQP8的丰度迅速增加其胆小管膜的水通透性。于是有人提出相反的过程，即胆小管AQP8表达降低是否会导致胆汁淤积的发生。在几种胆汁淤积实验模型中的研究，如肝外阻塞性胆汁淤积、雌激素诱导的胆汁淤积和脓毒症诱导的胆汁淤积，均表明肝细胞AQP8的蛋白表达受损。此外，对胆小管质膜的生物物理研究显示，与AQP8蛋白下调相关的水通透性降低。肝细胞溶质转运体和AQP8的联合改变会阻碍渗透梯度与胆小管水流的有效耦合。因此，胆汁淤积可能是溶质转运受损和水通透性降低共同作用的结果。
