Gentry-Nielsen M J, Preheim L C, Lyman K N, McDonough K H, Potter B J
Departments of Internal Medicine and Medical Microbiology and Immunology, Creighton University School of Medicine, University of Nebraska Medical Center and VA Medical Center, Omaha, NE 68105, USA.
Alcohol. 2001 Feb;23(2):71-81. doi: 10.1016/s0741-8329(00)00130-0.
With alcoholism, there are marked disturbances in iron homeostasis that are linked to alterations in serum transferrin and ferritin concentrations. This study identifies rat models of alcohol abuse that closely mimic these disturbances. Male rats were placed in one of the following three protocols: (1) pair-feeding of liquid diets for 1-8 weeks; (2) agar-block feeding for 8 weeks; or (3) generation of cirrhosis with CCl(4). Serum samples were analyzed for ferritin, transferrin, and iron levels, and the transferrin iron saturation and ferritin/transferrin ratios were calculated. Liver iron concentrations were also determined. Serum transferrin levels were elevated in animals fed alcohol for 8 weeks in pair-feeding and agar-block feeding protocols, but reduced in rats with cirrhosis. Serum ferritin concentration was reduced in rats fed ethanol in the liquid diet, but increased in rats consuming ethanol in agar blocks, in rats pair-fed the liquid control diet, and in rats with cirrhosis. This finding was mirrored by liver nonheme iron concentrations in all experimental groups, but not in the corresponding control groups. Serum iron levels were significantly elevated only in rats fed the liquid control diet. There was a progressive decrease in transferrin iron saturation and ferritin/transferrin ratios for animals fed ethanol in the liquid diet, but not when ethanol was ingested from agar blocks. The development of cirrhosis resulted in elevated liver iron concentrations and doubled ferritin/transferrin ratios. It is concluded that these models may be used to study disturbances in iron homeostasis that occur during alcohol abuse and the (subsequent) development of liver disease.
酒精中毒时，铁稳态会出现明显紊乱，这与血清转铁蛋白和铁蛋白浓度的改变有关。本研究确定了能紧密模拟这些紊乱的酒精滥用大鼠模型。雄性大鼠被分为以下三种方案之一：（1）液体饮食配对喂养1 - 8周；（2）琼脂块喂养8周；或（3）用四氯化碳诱导肝硬化。分析血清样本中的铁蛋白、转铁蛋白和铁水平，并计算转铁蛋白铁饱和度和铁蛋白/转铁蛋白比值。还测定了肝脏铁浓度。在配对喂养和琼脂块喂养方案中，喂养酒精8周的动物血清转铁蛋白水平升高，但肝硬化大鼠的血清转铁蛋白水平降低。液体饮食喂养乙醇的大鼠血清铁蛋白浓度降低，但琼脂块摄入乙醇的大鼠、配对喂养液体对照饮食的大鼠以及肝硬化大鼠的血清铁蛋白浓度升高。所有实验组肝脏非血红素铁浓度都反映了这一发现，但相应对照组未出现这种情况。仅液体对照饮食喂养的大鼠血清铁水平显著升高。液体饮食喂养乙醇的动物转铁蛋白铁饱和度和铁蛋白/转铁蛋白比值逐渐降低，但从琼脂块摄入乙醇时则不然。肝硬化的发展导致肝脏铁浓度升高，铁蛋白/转铁蛋白比值翻倍。结论是，这些模型可用于研究酒精滥用期间发生的铁稳态紊乱以及肝病的（后续）发展。
