Stuart Katherine Anne, Anderson Gregory Jon, Frazer David Michael, Murphy Therese Luna, Powell Lawrie William, Fletcher Linda Maria, Crawford Darrell Henry
Department of Gastroenterology and Hepatology, Princess Alexandra Hospital, Brisbane, Australia.
Hepatology. 2004 Feb;39(2):492-9. doi: 10.1002/hep.20038.
Hepatic hemosiderosis and increased iron absorption are common findings in cirrhosis. It has been proposed that a positive relation exists between intestinal iron absorption and the development of hepatic hemosiderosis. The current study investigated the duodenal expression of the iron transport molecules divalent metal transporter 1 (DMT1 [IRE]), iron-regulated gene 1 (Ireg1 [ferroportin]), hephaestin, and duodenal cytochrome b (Dyctb) in 46 patients with cirrhosis and 20 control subjects. Total RNA samples were extracted from duodenal biopsy samples and the expression of the iron transport genes was assessed by ribonuclease protection assays. Expression of DMT1 and Ireg1 was increased 1.5 to 3-fold in subjects with cirrhosis compared with iron-replete control subjects. The presence of cirrhosis per se and serum ferritin (SF) concentration were independent factors that influenced the expression of DMT1. However, only SF concentration was independently associated with Ireg1 expression. In cirrhosis, the expression of DMT1 and Ireg1 was not related to the severity of liver disease or cirrhosis type. There was no correlation between the duodenal expression of DMT1 and Ireg1 and the degree of hepatic siderosis. In conclusion, the presence of cirrhosis is an independent factor associated with increased expression of DMT1 but not Ireg1. The mechanism by which cirrhosis mediates this change in DMT1 expression has yet to be determined. Increased expression of DMT1 may play an important role in the pathogenesis of cirrhosis-associated hepatic iron overload.
肝含铁血黄素沉着症和铁吸收增加是肝硬化的常见表现。有人提出肠道铁吸收与肝含铁血黄素沉着症的发生之间存在正相关关系。本研究调查了46例肝硬化患者和20例对照者十二指肠中铁转运分子二价金属转运体1（DMT1[IRE]）、铁调节基因1（Ireg1[铁转运蛋白]）、铁氧化还原蛋白和十二指肠细胞色素b（Dyctb）的表达。从十二指肠活检样本中提取总RNA样本，并通过核糖核酸酶保护试验评估铁转运基因的表达。与铁充足的对照者相比，肝硬化患者中DMT1和Ireg1的表达增加了1.5至3倍。肝硬化本身的存在和血清铁蛋白（SF）浓度是影响DMT1表达的独立因素。然而，只有SF浓度与Ireg1表达独立相关。在肝硬化中，DMT1和Ireg1的表达与肝病严重程度或肝硬化类型无关。DMT1和Ireg1的十二指肠表达与肝铁沉着程度之间没有相关性。总之，肝硬化的存在是与DMT1表达增加相关的独立因素，但与Ireg1无关。肝硬化介导DMT1表达这种变化的机制尚待确定。DMT1表达增加可能在肝硬化相关肝铁过载的发病机制中起重要作用。
