IRON AND THE LIVER
IRON AND THE LIVER
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DOI：
10.1097/00000441-199101000-00006
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发表时间：
1991-01-01
影响因子：
3.1
通讯作者：
BONKOVSKY, HL
中科院分区：
文献类型：
--
作者：
BONKOVSKY, HL
铁是生命所必需的，但铁过量是有毒的，可能致命。 肝脏是铁储存的主要部位，特别容易受到铁过载的损伤，特别是当铁在肝细胞中积累时（如原发性血色病）。 铁可以通过几种形式和几种途径被肝脏吸收，包括：（1）二铁或单铁转铁蛋白或铁蛋白的受体介导的内吞作用，（2）铁从转铁蛋白的还原和载体促进的内化，而不内化转铁蛋白的蛋白质部分，（3）低分子量、非蛋白质结合形式的铁的产电摄取，以及（4）从血红素-白蛋白、血红素-血红素结合蛋白或血红蛋白-触珠蛋白复合物中摄取血红素。 通常，途径2可能是肝细胞摄取铁的主要途径。 铁以铁蛋白壳的核心和含铁血黄素的形式储存在肝脏中，含铁血黄素是一种来源于富铁铁蛋白的不溶性产物。 肝细胞中的铁刺激铁蛋白mRNA的翻译并抑制转铁蛋白和转铁蛋白受体的DNA转录。 慢性肝铁超载的主要病理效应是：（1）纤维化和肝硬化，（2）迟发性皮肤卟啉症，（3）肝细胞癌。 虽然确切的发病机制仍然未知，铁可能会产生这些和其他毒性作用，通过增加氧化应激和溶酶体不稳定性。 在诊断和治疗铁过载的积极努力是必不可少的，因为铁的病理影响是完全可以预防的早期强有力的铁去除和预防铁的再积累。
Iron is essential for life, but iron overload is toxic and potentially fatal. The liver is a major site of iron storage and is particularly susceptible to injury from iron overload, especially when (as in primary hemochromatosis) the iron accumulates in hepatocytes. Iron can be taken up by the liver in several forms and by several pathways including: (1) receptor-mediated endocytosis of diferric or monoferric transferrin or ferritin, (2) reduction and carrier-facilitated internalization of iron from transferrin without internalization of the protein moiety of transferrin, (3) electrogenic uptake of low molecular weight, non-protein bound forms of iron, and (4) uptake of heme from heme-albumin, heme-hemopexin, or hemoglobin-haptoglobin complexes. Normally, pathway 2 is probably the major one for uptake of iron by hepatocytes. Iron is stored in the liver in the cores of ferritin shells and as hemosiderin, an insoluble product derived from iron-rich ferritin. Iron in hepatocytes stimulates translation of ferritin mRNA and represses transcription of DNA for transferrin and transferrin receptors. The major pathologic effects of chronic hepatic iron overload are: (1) fibrosis and cirrhosis, (2) porphyria cutanea tarda, and (3) hepatocellular carcinoma. Although precise pathogenetic mechanisms remain unknown, iron probably produces these and other toxic effects by increasing oxidative stress and lysosomal lability. Vigorous efforts at diagnosis and treatment of iron overload are essential since the pathologic effects of iron are totally preventable by early vigorous iron removal and prevention of iron re-accumulation.