Van Eyken P, Sciot R, Desmet V
Laboratorium voor Histochemie en Cytochemie, Universitair Ziekenhuis St. Rafaël, Leuven, Belgium.
Lab Invest. 1988 Jul;59(1):52-9.
The development of the intrahepatic bile ducts was studied in rats from day 12 of gestation until 10 days of age using three antibodies directed against cytokeratins in an immunohistochemical procedure on paraffin-embedded liver tissue. In adult rat liver, both hepatocytes and bile ducts were stained by the monoclonal anti-cytokeratin no. 8, whereas two polyclonal antibodies stained bile ducts only. Hepatocytes in developing rat liver were stained by monoclonal anti-cytokeratin no. 8 from day 12 of gestation on. On day 16, cells strongly immunoreactive for cytokeratin no. 8 were observed in a string of pearl-like arrangement around large vascular branches close to the liver hilum. Over the following days, similar structures appeared throughout the liver. Gradually, lumina were formed in these structures, again starting at the liver hilum and resulting in the formation of individual bile ducts. Immunoreactivity with the polyclonal antibodies was first detected in some of the string of pearl-like structures on day 19 and gradually increased until the intensity observed in adult rat liver was reached on day 1 after birth. Even on day 10, portal spaces still revealed more bile duct branches, rings of cells strongly positive for cytokeratin no. 8 and weakly positive with the polyclonal antibodies were present. It is concluded that the intrahepatic bile ducts develop from hepatocytes. The cells closest to large vascular spaces first become strongly positive for cytokeratin no. 8 and only later on acquire additional ("bile duct type") cytokeratins. This process starts at the liver hilum and spreads through the liver. Even at 10 days of age the bile duct system is still immature: around the smaller portal vein branches, rings of cells are still undergoing transformation into bile duct type cells. These data might be useful for reevaluation of pathologic phenomena.
利用三种针对细胞角蛋白的抗体，采用免疫组织化学方法，对石蜡包埋的肝组织进行研究，观察了从妊娠第12天到出生后10天大鼠肝内胆管的发育情况。在成年大鼠肝脏中，单克隆抗细胞角蛋白8号抗体可使肝细胞和胆管均染色，而两种多克隆抗体仅使胆管染色。从妊娠第12天起，发育中的大鼠肝脏中的肝细胞就被单克隆抗细胞角蛋白8号抗体染色。在第16天，在靠近肝门的大血管分支周围观察到呈串珠状排列的、对细胞角蛋白8号有强免疫反应性的细胞。在接下来的几天里，类似结构出现在整个肝脏中。这些结构逐渐形成管腔，同样从肝门开始，最终形成单个胆管。多克隆抗体的免疫反应性在第19天首次在一些串珠状结构中检测到，并逐渐增强，直至出生后第1天达到成年大鼠肝脏中观察到的强度。即使在出生后第10天，门管区仍可见更多的胆管分支，存在对细胞角蛋白8号呈强阳性且对多克隆抗体呈弱阳性的细胞环。结论是肝内胆管由肝细胞发育而来。最靠近大血管间隙的细胞首先对细胞角蛋白8号呈强阳性，随后才获得额外的（“胆管型”）细胞角蛋白。这个过程从肝门开始并扩散至整个肝脏。即使在出生后10天，胆管系统仍不成熟：在较小的门静脉分支周围，细胞环仍在向胆管型细胞转变。这些数据可能有助于对病理现象进行重新评估。
