Park C H, Bacon B R, Brittenham G M, Tavill A S
Department of Pathology, Case Western Reserve University School of Medicine, Cleveland Metropolitan General Hospital, Ohio.
Lab Invest. 1987 Nov;57(5):555-63.
Serial light microscopic and ultrastructural studies were performed in rats with experimental iron overload produced by dietary supplementation with carbonyl (elemental) iron over a 12-month period. Hepatic iron increased rapidly to concentrations approximately 40 to 90 times those of control rats by 3 months. Within the liver, iron deposition was initially confined to periportal (zone 1) hepatocytes but subsequently extended to midzonal (zone 2) and centrilobular (zone 3) hepatocytes. Reticuloendothelial cell deposits of iron increased gradually and became prominent after 3 months. At this time, morphologic evidence of hepatocellular injury was mild and subtle with occasional foci of spotty necrosis and ultrastructural subcellular organelle damage. By 8 months, iron deposition was massive. Portal areas were enlarged with collections of iron-loaded macrophages and increased collagenous tissue. This portal fibrous tissue extended between periportal (zone 1) hepatocytes at sites of maximal iron deposition and around iron-loaded Kupffer cells and macrophages. At 12 months, the periportal (zone 1) fibrosis was more pronounced. These serial morphologic studies are the first to demonstrate the production of hepatic fibrosis by chronic dietary iron overload. This experimental model may reproduce important components of the pathophysiologic sequence of chronic liver damage seen in iron overload states in humans.
对通过在12个月期间膳食补充羰基（元素）铁产生实验性铁过载的大鼠进行了系列光学显微镜和超微结构研究。到3个月时，肝脏铁含量迅速增加到对照大鼠的约40至90倍。在肝脏内，铁沉积最初局限于门周（1区）肝细胞，但随后扩展到中区（2区）和小叶中心（3区）肝细胞。网状内皮细胞铁沉积逐渐增加，并在3个月后变得明显。此时，肝细胞损伤的形态学证据轻微且不明显，偶尔有散在坏死灶和超微结构亚细胞器损伤。到8个月时，铁沉积大量增加。门管区扩大，有铁负荷巨噬细胞聚集和胶原组织增加。这种门管纤维组织在铁沉积最多的部位在门周（1区）肝细胞之间以及围绕铁负荷的库普弗细胞和巨噬细胞延伸。在12个月时，门周（1区）纤维化更明显。这些系列形态学研究首次证明了慢性膳食铁过载可导致肝纤维化。该实验模型可能重现人类铁过载状态下慢性肝损伤病理生理过程的重要组成部分。
