Okayasu T, Tochimaru H, Hyuga T, Takahashi T, Takekoshi Y, Li Y, Togashi Y, Takeichi N, Kasai N, Arashima S
Department of Child Health, Hokkaido University of Education, Sapporo, Japan.
Pediatr Res. 1992 Mar;31(3):253-7. doi: 10.1203/00006450-199203000-00011.
The copper concentrations in organs of developing Long-Evans Cinnamon (LEC) rats (2 d to 13 mo) were measured to elucidate the pathogenesis of their hereditary hepatitis. Hepatic copper contents of LEC rats were significantly higher than those of control rats (26 to 92 times higher). The subcellular distribution of hepatic copper indicated that the nuclear and large granular fractions had been saturated and the cytosol fraction contained about 70% of all the hepatic copper in LEC rats. The serum concentrations of copper and ceruloplasmin were significantly lower than those of control rats from the 4th wk (10-12% and 5-19%, respectively). Copper contents in kidney of LEC rats did not exhibit an increase over those of control rats until 12 wk, but then increased to nearly 40 times higher during fulminant hepatic failure. Accumulation of copper was not detected in the brain or small intestines of LEC rats until 13 mo. The hepatic copper concentration, its subcellular distribution, and serum copper concentration of F1 rats (LEC x Long-Evans Agouti) exhibited the same levels as those of Long-Evans Agouti rats. In addition to their similarity concerning inheritance of autosomal recessive means and clinical course, we found causality relating copper accumulation to the pathogenesis of the disease. We propose that LEC rats will be the most promising animal model for the study of Wilson's disease.
为阐明遗传性肝炎的发病机制，我们测定了发育中的Long-Evans Cinnamon（LEC）大鼠（2日龄至13月龄）各器官中的铜浓度。LEC大鼠肝脏中的铜含量显著高于对照大鼠（高出26至92倍）。肝脏铜的亚细胞分布表明，LEC大鼠的细胞核和大颗粒部分已饱和，胞质部分约占肝脏总铜含量的70%。从第4周起，LEC大鼠血清中的铜和铜蓝蛋白浓度显著低于对照大鼠（分别为对照大鼠的10 - 12%和5 - 19%）。LEC大鼠肾脏中的铜含量在12周前未高于对照大鼠，但在暴发性肝衰竭期间增加至近40倍。直到13月龄，在LEC大鼠的脑或小肠中均未检测到铜的蓄积。F1大鼠（LEC×Long-Evans Agouti）的肝脏铜浓度、亚细胞分布及血清铜浓度与Long-Evans Agouti大鼠相同。除了在常染色体隐性遗传方式和临床病程方面具有相似性外，我们还发现铜蓄积与疾病发病机制之间存在因果关系。我们认为LEC大鼠将成为研究威尔逊病最有前景的动物模型。
