Pradhan-Sundd Tirthadipa, Monga Satdarshan Pal
Department of Pathology, University of Pittsburgh School of Medicine, Pittsburgh, PA, USA.
Gene Expr. 2019 Apr 18;19(2):69-87. doi: 10.3727/105221619X15469715711907. Epub 2019 Jan 15.
The term blood-bile barrier (BBlB) refers to the physical structure within a hepatic lobule that compartmentalizes and hence segregates sinusoidal blood from canalicular bile. Thus, this barrier provides physiological protection in the liver, shielding the hepatocytes from bile toxicity and restricting the mixing of blood and bile. BBlB is primarily composed of tight junctions; however, adherens junction, desmosomes, gap junctions, and hepatocyte bile transporters also contribute to the barrier function of the BBlB. Recent findings also suggest that disruption of BBlB is associated with major hepatic diseases characterized by cholestasis and aberrations in BBlB thus may be a hallmark of many chronic liver diseases. Several molecular signaling pathways have now been shown to play a role in regulating the structure and function and eventually contribute to regulation of the BBlB function within the liver. In this review, we will discuss the structure and function of the BBlB, summarize the methods to assess the integrity and function of BBlB, discuss the role of BBlB in liver pathophysiology, and finally, discuss the mechanisms of BBlB regulation. Collectively, this review will demonstrate the significance of the BBlB in both liver homeostasis and hepatic dysfunction.
血胆屏障（BBlB）这一术语指的是肝小叶内的一种物理结构，它将窦状隙血液与胆小管胆汁分隔开来。因此，该屏障在肝脏中提供生理保护，使肝细胞免受胆汁毒性影响，并限制血液与胆汁的混合。血胆屏障主要由紧密连接组成；然而，黏着连接、桥粒、缝隙连接以及肝细胞胆汁转运体也对血胆屏障的功能有贡献。最近的研究结果还表明，血胆屏障的破坏与以胆汁淤积为特征的主要肝脏疾病相关，血胆屏障的异常可能是许多慢性肝病的一个标志。现已证明，几种分子信号通路在调节血胆屏障的结构和功能方面发挥作用，并最终有助于调节肝脏内血胆屏障的功能。在本综述中，我们将讨论血胆屏障的结构和功能，总结评估血胆屏障完整性和功能的方法，探讨血胆屏障在肝脏病理生理学中的作用，最后讨论血胆屏障的调节机制。总体而言，本综述将证明血胆屏障在肝脏稳态和肝功能障碍中的重要性。
