Pathogenetic Significance of Serum Glycoprotein Abnormality in Alcoholic Liver Injury.

酒精性肝损伤中血清糖蛋白异常的发病机制。

基本信息

批准号：
01480231
负责人：
TAKADA Akira
金额：
$ 4.29万
依托单位：
Kanazawa Medical University
依托单位国家：
日本
项目类别：
Grant-in-Aid for General Scientific Research (B)
财政年份：
1989
资助国家：
日本
起止时间：
1989 至 1990
项目状态：
已结题

项目摘要

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.

在人类和大鼠酒精肝损伤（ALI）中，转铁蛋白（TF）在气囊的肝细胞中都被强烈染色。这种变化与血清TF的微观分别（MCHT）的出现有关。通过免疫电子显微镜，保留在高尔基体中的TF。掺入 ^<14> c-戊糖和 ^3H-亮氨酸，尤其是Fucose，降低了血清TF的速率，而来自Ali的高尔基体的这些标记的分泌也延迟了。通过使用 ^<35> s-methionine在培养的肝细胞中的脉冲练习标记分析，建议在ALI中延迟TF的成熟。通过蛋白质印迹清楚地检测到血清TF和α-抗抗蛋白蛋白的MCHT，但没有其他糖蛋白。 MCHT通过治疗唾液酸酶消失，表明TF的MCHT是由硅酸变化引起的。在严重的肝病中，例如肝肝硬化的代偿性疾病，也发现了TF的MCHT。但是，这种疾病的等电聚焦模式与ALI不同。即使在唾液酸处理的血清中也发现了差异，这表明TF的MCHT可能与肝细胞膜上Asialo-糖蛋白受体的减少无关。开发了一种检测血清TF的MCHT的简单方法。使用这种方法，在100名ALI患者中，有73％发现了TF的MCHT。 MCHT在严重类型的ALI中更常见。但是，在任何酗酒胰腺炎和没有肝病的饮酒者的情况下都找不到TF的MCHT。这些结果表明，MCHT是酒精特异性肝损伤的标志，但不是慢性酒精中毒。