Faculty of Medicine, University of Coimbra, Coimbra, Portugal.
Eur J Gastroenterol Hepatol. 2012 Oct;24(10):1158-65. doi: 10.1097/MEG.0b013e328355cfd0.
Hepcidin plays a crucial role in iron metabolism, preventing its absorption at the basolateral enterocyte membrane. Hepcidin regulation is complex and regulated at the transcriptional level. The relation between iron overload and alcoholic liver disease is well known, but its mechanism is not clear. We present an observational, case-control study, aimed at evaluating the effects of alcohol on the expression of hepcidin in human participants. We intended to assess whether iron overload related to alcohol ingestion was caused by hepcidin-impaired expression by determining hepcidin mRNA expression and relating it to iron stores, both in alcoholic patients and in normal controls.
We compared liver hepcidin mRNA expression between 25 active drinkers with alcoholic liver disease, without cirrhosis, and 20 healthy controls. All individuals were evaluated for HFE mutations, complete blood count, coagulation, glucose, kidney function, liver function, viral hepatitis, C-reactive protein, interleukin 6, tumor necrosis factor α, and serum iron, ferritin, and transferrin saturation. Total RNA was isolated from liver samples, cDNA was obtained by reverse transcription, and hepatic expression levels of hepcidin were determined by real-time PCR using the comparative Ct method (2(-ΔΔCt)).
Serum ferritin and transferrin saturation were significantly higher in patients. Hepcidin was downregulated in patients compared with the controls by a mean factor of -0.44 (log10 2(-ΔΔCt)) (P=0.009). Hepcidin expression was not significantly different between the several grades of fibrosis, necroinflammatory activity, and liver iron stores. Heavy alcohol consumption caused the highest hepcidin mRNA suppression. The hepcidin mRNA expression/serum ferritin ratio was significantly lower in alcoholic patients (P<0.0001).
Hepcidin liver expression is inappropriately low in alcoholic patients with active alcoholism and preserved hepatic function, and we conclude that this is the mechanism for alcohol consumption-associated iron overload in humans.
铁调素在铁代谢中起着至关重要的作用，可防止其在基底外侧肠细胞膜处被吸收。铁调素的调节非常复杂，可在转录水平上进行调节。铁过载与酒精性肝病之间的关系众所周知，但具体机制尚不清楚。我们进行了一项观察性病例对照研究，旨在评估酒精对人类参与者铁调素表达的影响。我们旨在通过确定铁调素 mRNA 表达并将其与铁储存相关联，来评估与酒精摄入相关的铁过载是否是由于铁调素表达受损引起的，这种情况既发生在酒精性肝病患者中，也发生在正常对照组中。
我们比较了 25 例有活性饮酒史的酒精性肝病（无肝硬化）患者和 20 例健康对照者的肝铁调素 mRNA 表达。对所有个体均进行 HFE 基因突变、全血细胞计数、凝血、血糖、肾功能、肝功能、病毒性肝炎、C 反应蛋白、白细胞介素 6、肿瘤坏死因子 α 和血清铁、铁蛋白和转铁蛋白饱和度检测。从肝组织样本中分离总 RNA，通过反转录获得 cDNA，并采用实时 PCR 技术（采用 2(-ΔΔCt) 法）测定肝组织中铁调素的表达水平。
患者的血清铁蛋白和转铁蛋白饱和度明显更高。与对照组相比，患者的铁调素表达下调，下调幅度的平均值为 -0.44（log10 2(-ΔΔCt)）（P=0.009）。铁调素表达在不同纤维化程度、坏死性炎症活动度和肝铁储存之间无显著差异。大量饮酒导致铁调素 mRNA 抑制作用最强。酒精性肝病患者的铁调素 mRNA 表达/血清铁蛋白比值明显降低（P<0.0001）。
铁调素在有活性饮酒且肝功能正常的酒精性肝病患者中的肝脏表达不适当降低，我们推断这是人类饮酒相关铁过载的机制。
