Zhang H, Loney L A, Potter B J
Division of Liver Diseases, Mount Sinai School of Medicine, New York, New York.
Alcohol Clin Exp Res. 1993 Apr;17(2):394-400. doi: 10.1111/j.1530-0277.1993.tb00782.x.
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 with 59Fe 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 degrees C and 4 degrees 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 chow-fed 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/10(6) cells, 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).(ABSTRACT TRUNCATED AT 250 WORDS)
众所周知,酒精滥用会扰乱人体铁稳态,并与血清铁蛋白水平升高有关。我们之前已经表明,大鼠肝细胞中的乙醇代谢与该细胞对铁蛋白摄取的立即减少有关。在本研究中,我们研究了用利伯-德卡利液体酒精饮食进行配对喂养对大鼠肝细胞摄取铁蛋白的影响。大鼠肝脏铁蛋白在体内用59Fe进行放射性标记,并通过传统技术分离。大鼠用利伯-德卡利液体酒精饮食配对喂养4至6周。通过胶原酶灌注从其肝脏中分离出的肝细胞,在37℃和4℃下于L-15培养基中与[59Fe]铁蛋白一起孵育,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作用。在这些动物以及一组可比的正常喂食大鼠的血清和肝细胞中测量铁蛋白和铁参数。酒精喂养大鼠的肝细胞摄取铁蛋白的速率明显快于其配对喂养的对照(0.743±0.061对0.540±0.042 ng/min/10(6)细胞,p<0.05)。然而,食用利伯-德卡利对照饮食的大鼠肝细胞铁蛋白摄取率低于正常喂食的动物(为对照值的79.3±8.1%,p<0.01)。在100 mM乙醇中对细胞进行体外孵育时,与配对喂养的对照相比,酒精喂养大鼠的肝细胞对铁蛋白摄取的抑制作用较小(抑制率为11±7.1%,而对照为43.6±10.7%,p<0.05)。(摘要截断于250字)