Tag C G, Weiskirchen S, Hittatiya K, Tacke F, Tolba R H, Weiskirchen R
Institute of Molecular Pathobiochemistry, Experimental Gene Therapy and Clinical Chemistry, RWTH University Hospital Aachen, Aachen, Germany.
Institute of Pathology, University Hospital Bonn, Bonn, Germany.
Lab Anim. 2015 Apr;49(1 Suppl):70-80. doi: 10.1177/0023677214567748.
The induction of experimental obstructive cholestasis is a reliable model for cholestatic liver diseases in rodents. Bile duct ligation (BDL) in mice provokes typical time-dependent morphological and structural changes in the liver, ranging from liver cell injury and elevated serum enzyme levels after several days, to a severe inflammatory response in the liver after 5-7 days, up to an advanced hepatic fibrosis as soon as three to four weeks after surgical ligation of the common biliary duct. Upon BDL induction, hepatic stellate cells become activated and transdifferentiate into myofibroblasts that produce extracellular matrix proteins such as collagen. In principle, the periportal fibrosis induced by BDL in rat livers is reversible. After the relief of a biliary obstruction, the liver has the capacity to revert to a nearly normal histological architecture and a fully normal biochemical function. When BDL surgery is performed by an experienced scientist, this model has very high reproducibility among all fibrotic models. All these factors corroborate the outstanding value of this model for basic and translational research in biomedicine and hepatology. Nevertheless, this model can result in significant variations when surgery is carried out by untrained personnel or when unconscious modifications are implemented that affect the quality of the intervention. A detailed protocol is provided here for the provision of reliable and reproducible BDL in mice.
实验性梗阻性胆汁淤积的诱导是啮齿动物胆汁淤积性肝病的可靠模型。小鼠胆管结扎（BDL）会引发肝脏典型的时间依赖性形态和结构变化，从数天后的肝细胞损伤和血清酶水平升高，到5 - 7天后肝脏的严重炎症反应，直至胆总管手术结扎三到四周后出现晚期肝纤维化。在BDL诱导后，肝星状细胞被激活并转分化为产生细胞外基质蛋白（如胶原蛋白）的肌成纤维细胞。原则上，大鼠肝脏中由BDL诱导的门周纤维化是可逆的。解除胆道梗阻后，肝脏有能力恢复到几乎正常的组织学结构和完全正常的生化功能。当由经验丰富的科学家进行BDL手术时，该模型在所有纤维化模型中具有非常高的可重复性。所有这些因素都证实了该模型在生物医学和肝病学基础及转化研究中的突出价值。然而，当由未经培训的人员进行手术或实施影响干预质量的无意识修改时，该模型可能会导致显著差异。此处提供了一份详细方案，用于在小鼠中提供可靠且可重复的BDL。
