Pathogenetic Significance of Serum Glycoprotein Abnormality in Alcoholic Liver Injury.

在人和大鼠酒精性肝损伤(ALI)模型中，转铁蛋白(Tf)在气球状肝细胞中呈强阳性染色。这种改变与血清转铁蛋白的微异质性(MCHT)的出现有关。免疫电子显微镜观察，Tf滞留在高尔基体内。ALI时，~(14)C-岩藻糖和~3H-亮氨酸(尤其是岩藻糖)对血清Tf的掺入率降低，高尔基体对这些标记的分泌延迟。用~(35)&GT；S-蛋氨酸对培养的肝细胞进行脉冲追逐标记分析，提示在ALI时TF的成熟可能被延缓。Western blotting检测到血清转铁蛋白和α-抗胰蛋白酶的MCHT，但不能检测到其他糖蛋白的MCHT。唾液酸酶处理使Tf的MCHT消失，说明Tf的MCHT是由唾液酸变化引起的。在严重肝病中，如失代偿期肝硬变，也可发现Tf的MCHT。然而，该病的等电聚焦模式与ALI不同。即使在唾液酸处理的血清中，这种差异也存在，提示Tf的MCHT可能与肝细胞膜去唾液酸糖蛋白受体的减少无关。建立了一种简便的检测血清转铁蛋白MCHT的方法。在100例ALI患者中，Tf的MCHT发生率为73%。MCHT多见于重症ALI。但在酒精性胰腺炎和无肝病的酗酒者中均未发现Tf的MCHT。这些结果表明，MCHT是酒精性肝损伤的标志，但不是慢性酒精中毒的标志。

Both in human and rat alcoholic liver injury (ALI), transferrin (TF) was strongly stained in the ballooned hepatocytes. This change was related to the appearance of microheterogeneity (MCHT) of serum TF. By immunoelectron microscopy, Tf retained in the Golgi apparatus. Incorporation rate of ^<14>C-fucose and ^3H-leucine, especially fucose, to serum Tf decreased, and secretion of these labels from the Golgi apparatus delayed in ALI. By the Pulse-chase labeling analysis in cultured hepatocytes using ^<35>S-methionine, it was suggested that maturation of Tf may be retarded in ALI. MCHT of serum Tf and alphal-antitrypsin, but not other glycoproteins, was clearly detected by Western blotting. MCHT disappeared by the treatment of sialidase, indicating that MCHT of TF was caused by changes in silalic acid. In severe liver disease, such as decompensated liver cirrhosis, MCHT of TF was also found. However, the isoelectric focusing pattern of such disease was different from that of ALI. The differences was found even in the sialic acid-treated serum, suggesting that MCHT of Tf may not be related to the decrease of asialo-glycoprotein receptor on the hepatocyte membrane. A simple method to detect MCHT of serum TF was developed. Using this method, MCHT of TF was found in 73 % of 100 patients with ALI. MCHT was more frequently found in severe type of ALI. However, MCHT of TF could not found in any case of alcoholic pancreatitis and heavy drinkers without liver disease. These results suggest that MCHT is a marker of alcohol specific liver injury, but not chronic alcoholism.