Masson R, Roome N O
Department of Drug Safety, Synthélabo Recherche, Gargenville, France.
Toxicol Pathol. 1997 May-Jun;25(3):308-16. doi: 10.1177/019262339702500308.
In a review of the toxicological studies performed in our laboratory during the period 1986-1995, we occasionally observed significant iron overloading in the liver. Liver tissue was examined by light and electron microscopy, and the results were analyzed by sex and age (7, 9, 11, 19, 31, 59, and 111 wk). The intensity of iron overload increased with age: the accumulation began in pericanalicular siderosomes of periportal hepatocytes and extended progressively to the entire lobule and also to nonhepatocytic cells (Kupffer cells in sinusoids and macrophages around bile ducts in portal tracts) and occasionally with distortion of sinusoids by sideroblastic nodules and moderate enlargement of portal tracts in the oldest animals. No significant inflammatory infiltrates, degeneration, necrosis or fibrosis were noted. Hepatocyte pigmentation alone was prominent at 9 and 11 wk. The frequency of pigmentation of parenchymal and nonhepatocytic cells increased from 9 wk for females; in males, this was seen only at 111 wk. The intensity of pigmentation of nonhepatocytic cells versus parenchymal cells increased with aging. The frequency of those different types of iron overloading was higher for females up to 111 wk. The pathology of spontaneous iron overloading in the Sprague-Dawley rat, described here in spite of differences, has some similarities to that of human hereditary hemochromatosis.
在回顾我们实验室于1986年至1995年期间进行的毒理学研究时，我们偶尔观察到肝脏中铁显著过载。通过光学显微镜和电子显微镜检查肝组织，并按性别和年龄（7、9、11、19、31、59和111周）对结果进行分析。铁过载的强度随年龄增加：积累始于门周肝细胞的胆小管周围铁粒小体，并逐渐扩展至整个肝小叶，还扩展至非肝细胞（窦状隙中的库普弗细胞和门管区胆管周围的巨噬细胞），在最老的动物中偶尔会出现含铁粒幼细胞结节导致的窦状隙变形和门管区中度扩大。未观察到明显的炎性浸润、变性、坏死或纤维化。仅在9周和11周时肝细胞色素沉着较为突出。雌性从9周开始实质细胞和非肝细胞色素沉着的频率增加；雄性仅在111周时出现这种情况。非肝细胞与实质细胞色素沉着的强度随衰老而增加。在111周之前，雌性出现这些不同类型铁过载的频率更高。尽管存在差异，但此处描述的斯普拉格 - 道利大鼠自发性铁过载的病理学与人类遗传性血色素沉着症有一些相似之处。
