Simpson R J, Konijn A M, Lombard M, Raja K B, Salisbury J R, Peters T J
Department of Clinical Biochemistry, King's College School of Medicine and Dentistry, London, U.K.
J Pathol. 1993 Nov;171(3):237-44. doi: 10.1002/path.1711710313.
Tissue iron loading in hypotransferrinaemic (hpx/hpx) mice was investigated as a model for genetic (primary) haemochromatosis. Iron loading of liver preceded that in the pancreas and heart. One-year-old hpx/hpx mice showed iron staining in exocrine pancreas, liver parenchymal cells, and cardiac and intestinal smooth muscle cells. Iron-loaded macrophages were observed in all these tissues. Islets of Langerhans, biliary epithelial cells, and spleen were iron-free. The pancreas was fibrotic with massive macrophage infiltration and loss of secretory epithelium. Liver showed evidence of chronic inflammatory infiltration with increased collagen fibres in the parenchymal region but no cirrhosis. Serum aspartate aminotransferase activity and plasma glucose were increased in hpx/hpx compared with wild-type mice. Heavy iron loading with haemosiderin deposition in the liver could be demonstrated in hpx/hpx mice from 6 weeks of age. Heterozygous hypotransferrinaemic mice showed minor increases in liver iron stores at 6-12 weeks, but not at 1 year of age. Serum ferritin levels in heterozygous mice were also increased at 6-8 weeks of age. It was concluded that 1-year-old hpx/hpx mice showed evidence of liver and pancreatic damage secondary to tissue iron overload. The iron loading pattern and tissue damage showed some features which were distinct from those observed in haemochromatosis.
作为遗传性（原发性）血色素沉着症的模型，研究了低转铁蛋白血症（hpx/hpx）小鼠的组织铁负荷情况。肝脏的铁负荷先于胰腺和心脏。1岁的hpx/hpx小鼠在外分泌胰腺、肝实质细胞、心脏和肠道平滑肌细胞中出现铁染色。在所有这些组织中均观察到铁负荷的巨噬细胞。胰岛、胆管上皮细胞和脾脏未发现铁。胰腺纤维化，伴有大量巨噬细胞浸润和分泌上皮丧失。肝脏显示有慢性炎症浸润的证据，实质区域胶原纤维增加，但无肝硬化。与野生型小鼠相比，hpx/hpx小鼠的血清天冬氨酸转氨酶活性和血糖升高。在6周龄的hpx/hpx小鼠中即可证明肝脏中有大量铁负荷并伴有含铁血黄素沉积。杂合子低转铁蛋白血症小鼠在6-12周时肝脏铁储存略有增加，但1岁时未增加。杂合子小鼠在6-8周龄时血清铁蛋白水平也升高。结论是，1岁的hpx/hpx小鼠显示出组织铁过载继发的肝脏和胰腺损伤迹象。铁负荷模式和组织损伤表现出一些与血色素沉着症不同的特征。
