Bassett Mark L, Dahlstrom Jane E, Taylor Matthew C, Koina Mark E, Maxwell Lesley, Francis Douglas, Jain Sanjiv, McLean Allan J
Gastroenterology Unit, The Canberra Hospital, Canberra, Australia.
Exp Toxicol Pathol. 2003 Jul;55(1):11-6. doi: 10.1078/0940-2993-00296.
Hepatic sinusoidal endothelial cells form an important interface between the vascular system, represented by the sinusoids, and the space of Disse that surrounds the hepatocyte microvilli. This study aimed to assess the light microscopic and ultrastructural effects of acute exposure of hepatic sinusoidal endothelial cells to colloidal iron by injection of rats with iron polymaltose. Eight minutes after a single intravenous injection of iron polymaltose sinusoidal endothelial cells showed defenestration, and thickening and layering as assessed by transmission electron microscopy. Kupffer cells and stellate cells appeared activated. These changes were not observed in control animals, experiments using equivalent doses of maltose, or experiments using colloidal carbon except for Kupffer cell activation due to colloidal carbon. No significant light microscopic changes were seen in study or control animals. The findings indicate that acute exposure to colloidal iron causes changes in hepatic sinusoidal endothelial cells, stellate cells and Kupffer cells. This may be the result of a direct toxic effect of iron or increased production of reactive oxygen species. These observations suggest a possible mechanism for defenestration of sinusoidal endothelial cells in ageing and in disease states.
肝窦内皮细胞在以肝血窦为代表的血管系统与围绕肝细胞膜微绒毛的狄氏间隙之间形成了一个重要界面。本研究旨在通过给大鼠注射聚麦芽糖铁来评估肝窦内皮细胞急性暴露于胶体铁后的光学显微镜和超微结构效应。单次静脉注射聚麦芽糖铁8分钟后,透射电子显微镜观察显示肝血窦内皮细胞出现窗孔消失、增厚和分层。库普弗细胞和星状细胞似乎被激活。在对照动物、使用等量麦芽糖的实验或使用胶体碳的实验中,除了胶体碳导致库普弗细胞激活外,未观察到这些变化。在研究组或对照组动物中均未观察到明显的光学显微镜变化。这些发现表明,急性暴露于胶体铁会导致肝窦内皮细胞、星状细胞和库普弗细胞发生变化。这可能是铁的直接毒性作用或活性氧产生增加的结果。这些观察结果提示了衰老和疾病状态下肝窦内皮细胞窗孔消失的一种可能机制。