Abdel-Aziz G, Rescan P Y, Clement B, Lebeau G, Rissel M, Grimaud J A, Campion J P, Guillouzo A
INSERM U49, Unité de Recherches Hépatologiques, Hôpital Pontchaillou, Rennes, France.
J Pathol. 1991 Jun;164(2):167-74. doi: 10.1002/path.1711640211.
Collagens (I, III, and IV), fibronectin, and laminin were localized using the indirect immunoperoxidase technique 14 days after bile duct ligation, i.e., when extensive fibrosis and numerous neoformed bile ducts were observed. Extensive fibrous septa in enlarged portal spaces were stained for collagens I, III and IV, fibronectin, and laminin. Collagen IV and laminin were abundant around proliferative bile ducts. In addition, collagen IV was nearly continuous in the sinusoids. At the ultrastructural level, antigens were localized in the endoplasmic reticulum of several liver cell types. In portal spaces, bile duct cells and cells that form the transitional canal of Hering were strongly labelled for basement membrane components, particularly laminin, but not for collagens I and III and fibronectin, which were abundant in fibroblast-like cells. Inside the lobule, only Ito cells and, to a lesser extent, endothelial cells contained collagens, fibronectin, and laminin. Ito cells were found to be heavily stained for collagens III and IV, and laminin. Except for fibronectin, which was always abundant, precursors of extracellular matrix proteins were only slightly detectable in the endoplasmic reticulum of some hepatocytes, particularly those located close to altered areas. This study demonstrates that experimental extrahepatic cholestasis in the rat induces periportal fibrosis and continuous deposition of collagen IV in the sinusoids. Several cell types participate in the formation of extracellular matrix components, particularly bile duct cells and Ito cells, with a possible involvement of hepatocytes, thus suggesting that cholestasis provokes changes in the pattern of matrix protein production in liver cells.
在胆管结扎14天后，即观察到广泛纤维化和大量新生胆管时，采用间接免疫过氧化物酶技术对胶原蛋白（I、III和IV型）、纤连蛋白和层粘连蛋白进行定位。扩大的门管区中的广泛纤维间隔被染成I、III和IV型胶原蛋白、纤连蛋白和层粘连蛋白。增殖胆管周围胶原蛋白IV和层粘连蛋白丰富。此外，胶原蛋白IV在肝血窦中几乎连续存在。在超微结构水平上，抗原定位于几种肝细胞类型的内质网中。在门管区，胆管细胞和形成赫林管的细胞被强烈标记为基底膜成分，特别是层粘连蛋白，但I和III型胶原蛋白以及纤连蛋白未被标记，这些蛋白在成纤维细胞样细胞中丰富。在小叶内部，只有贮脂细胞以及程度较轻的内皮细胞含有胶原蛋白、纤连蛋白和层粘连蛋白。发现贮脂细胞被III和IV型胶原蛋白以及层粘连蛋白重度染色。除了始终丰富的纤连蛋白外，细胞外基质蛋白的前体仅在一些肝细胞的内质网中略有可检测到，特别是那些位于病变区域附近的肝细胞。本研究表明，大鼠实验性肝外胆汁淤积可诱导门周纤维化和胶原蛋白IV在肝血窦中的持续沉积。几种细胞类型参与细胞外基质成分的形成，特别是胆管细胞和贮脂细胞，肝细胞可能也参与其中，因此提示胆汁淤积会引发肝细胞中基质蛋白产生模式的变化。
