Effect of chronic alcohol feeding on hepatic iron status and ferritin uptake by rat hepatocytes.
Effect of chronic alcohol feeding on hepatic iron status and ferritin uptake by rat hepatocytes.
复制标题
慢性酒精喂养对大鼠肝细胞肝铁状态和铁蛋白摄取的影响。
DOI：
10.1111/j.1530-0277.1993.tb00782.x
复制
发表时间：
1993
期刊：
影响因子：
--
通讯作者：
Potter,BJ
中科院分区：
文献类型：
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作者：
Zhang,H;Loney,LA;Potter,BJ
众所周知，酗酒会扰乱人类的铁稳态，并与血清铁蛋白水平升高有关。我们之前已经证明，大鼠肝细胞中的乙醇代谢与该细胞摄取铁蛋白的立即减少有关。在本研究中，我们研究了配对喂养 Lieber-DeCarli 液体酒精饮食对大鼠肝细胞吸收铁蛋白的影响。大鼠肝脏铁蛋白在体内用 59 Fe 进行放射性标记，并通过常规技术分离。给大鼠配对喂养 Lieber-DeCarli 液体酒精饮食 4-6 周。通过胶原酶灌注从肝脏中分离出肝细胞，与 [59Fe] 铁蛋白在 L-15 培养基中于 37°C 和 4° 下孵育，以测量铁蛋白的摄取和结合。还研究了乙醇对这些肝细胞的体外影响。对这些动物和正常喂食大鼠的血清和肝细胞中的铁蛋白和铁参数进行了测量。酒精喂养的大鼠的肝细胞对铁蛋白的摄取率明显快于配对喂养的对照组（0.743 ± 0.061 vs. 0.540 ± 0.042 ng/min/106cells，p < 0.05）。然而，采用 Lieber-DeCarli 对照饮食的大鼠表现出比普通饲料喂养的大鼠更低的肝细胞铁蛋白摄取率（对照值的 79.3 ± 8.1%，p < 0.01）。在 100 mm 乙醇中体外培养细胞，导致酒精大鼠肝细胞对铁蛋白摄取的抑制程度低于配对喂养对照组（抑制程度为 11 ± 7.1%，对照组为 43.6 ± 10.7%，p < 0.05）。受体介导的铁蛋白与肝细胞的结合显示，酒精大鼠的饱和结合能力增加了 61%（15,820 ± 4950 分子/细胞 vs. 9798 ± 3622，p= 0.05）。培养基中乙醇的存在不会显着影响铁蛋白结合。尽管三组之间的血清铁值没有显着差异，但酒精喂养的大鼠中转铁蛋白浓度显着升高，导致转铁蛋白铁饱和度比对照组动物低得多。由于饮食对照的相应血清值介于酒精喂养的大鼠和食物喂养的动物之间，因此这些发现可能反映了流质饮食的饮食限制，而添加酒精会加剧这种限制。这些发现表明，长期饮酒后肝细胞对铁的吸收增加，这可能是由于铁蛋白受体增加所致。这种酒精治疗也会导致血清铁蛋白消耗的观察结果支持了这一点。然而，酒精喂养的大鼠中铁含量的降低表明，这可能是由于肝细胞对铁稳态变化和/或体内重新分布的反应所致。
Alcohol abuse is known to cause disturbances to iron homeostasis in man and is associated with elevated serum ferritin levels. We have previously shown that ethanol metabolism in the rat hepatocyte is associated with an immediate reduction in ferritin uptake by this cell. In this study we have examined the effect of pair‐feeding the Lieber‐DeCarli liquid alcohol diet on ferritin uptake by rat hepatocytes.Rat liver ferritin was radiolabeled with59Fe in vivo and isolated by conventional techniques. Rats were pair‐fed the Lieber‐DeCarli liquid alcoholic diet for 4–6 weeks. Hepatocytes, isolated from their livers by collagenase perfusion, were incubated with [59Fe]ferritin in L‐15 medium at 37°C and 4° to measure ferritin uptake and binding. The in vitro effect of ethanol on these hepatocytes was also studied. Ferritin and iron parameters were measured in the sera and hepatocytes of these animals and a comparable group of normal chowfed rats.The rate of ferritin uptake by hepatocytes from alcohol‐fed rats was significantly faster than that of their pair‐fed controls (0.743 ± 0.061 vs. 0.540 ± 0.042 ng/min/106cells,p< 0.05). However, the rats on Lieber‐DeCarli control diet exhibited a lower hepatocyte ferritin uptake rate than chow‐fed animals (79.3 ± 8.1% of the control values,p< 0.01). In vitro incubation of cells in 100 mm ethanol resulted in less inhibition of ferritin uptake by hepatocytes from alcoholic rats than from their pair‐fed controls (11 ± 7.1% inhibition vs. 43.6 ± 10.7% for controls,p< 0.05). Receptor‐mediated binding of ferritin to hepatocytes showed a 61% increase in saturable binding capacity for alcoholic rats (15,820 ± 4950 molecules/cell vs. 9798 ± 3622,p= 0.05). The presence of ethanol in the medium did not affect ferritin binding significantly.Although there was no significant difference in the serum iron values between all three groups, transferrin concentrations were markedly elevated in the alcohol‐fed rats, resulting in a much lower transferrin iron saturation than for the control animals. Because the corresponding serum values for the diet controls were intermediate between those for the alcohol‐fed rats and the chow‐fed animals, these findings may reflect dietary restriction by the liquid diet, which is exacerbated by the addition of alcohol.These findings suggest that there is increased iron uptake by the hepatocyte following chronic alcohol administration, which may be due to the increased ferritin receptors. This is supported by the observation that this alcohol treatment also causes a depletion of serum ferritin. However, the decreased iron content in the alcohol‐fed rats indicate that this may be due to a response to changes in iron homeostasis by the hepatocyte and/or redistribution in the body.