Pathogenetic Significance of Serum Glycoprotein Abnormality in Alcoholic Liver Injury.

在人和大鼠酒精性肝损伤（ALI）中，转铁蛋白（TF）在气球样肝细胞中强烈染色。这种变化与血清TF微异质性（MCHT）的出现有关。免疫电镜观察，Tf保留在高尔基体中。在<14>ALI中，^C-岩藻糖和^3 H-亮氨酸，尤其是岩藻糖，对血清Tf的掺入率降低，并且这些标记物从高尔基体的分泌延迟。用~（60）S-蛋氨酸对培养肝细胞进行Pulse-chase标记分析<35>，提示ALI时Tf的成熟可能受到阻滞。血清转铁蛋白和胰蛋白酶的MCHT，而不是其他糖蛋白，清楚地检测到蛋白质印迹。MCHT在唾液酸酶处理后消失，表明TF的MCHT是由唾液酸的变化引起的。严重肝病如失代偿期肝硬化也可出现TF的MCHT，但其等电聚焦模式与ALI不同。这种差异甚至在唾液酸处理的血清中也被发现，这表明Tf的MCHT可能与肝细胞膜上无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TF MCHT的方法。在100例急性肺损伤患者中，73%的患者存在TF的MCHT. MCHT多见于重型ALI。而在酒精性胰腺炎和无肝病的重度饮酒者中均未发现TF的MCHT。这些结果表明，MCHT是酒精特异性肝损伤的标志物，但不是慢性酒精中毒。

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.