Yano M, Sakamoto N, Takikawa T, Hayashi H
Third Department of Medicine, Nagoya University School of Medicine, Japan.
Nagoya J Med Sci. 1993 Mar;55(1-4):131-7.
It is well known that excess copper plays a role in the pathogenesis of Wilson's disease; however, the hepatic copper contents, determined either histochemically or biochemically, are not always correlated with the activity of Wilson's disease. To better understand copper-induced cytotoxicity, intrahepatocellular localization of copper was studied in five patients with Wilson's disease. The liver specimens were obtained by biopsy to confirm the clinical diagnosis of Wilson's disease before treatment. Neither hepatic copper content nor histochemical copper deposits were correlated with any of the biochemical indices studied. Energy-dispersion X-ray microanalysis was done on the nuclei, lysosomes and lysosome-free cytoplasm of hepatocytes. Lysosomes had the highest Cu X-ray intensity but no correlation was shown between the lysosomal copper content and biochemical indices. The nucleus/lysosome-free cytoplasm ratio of the copper content was correlated with the serum levels of aminotransferases. These results suggest that the copper increasing gradient from the lysosome-free cytoplasm to the nucleus is associated with hepatocyte necrosis, and probably causes irreversible nuclear damage.
众所周知，过量的铜在威尔逊氏病的发病机制中起作用；然而，通过组织化学或生物化学方法测定的肝脏铜含量并不总是与威尔逊氏病的活动相关。为了更好地理解铜诱导的细胞毒性，对五例威尔逊氏病患者肝细胞内铜的定位进行了研究。在治疗前通过活检获取肝脏标本以确诊威尔逊氏病。肝脏铜含量和组织化学铜沉积均与所研究的任何生化指标均无相关性。对肝细胞的细胞核、溶酶体和无溶酶体的细胞质进行了能量色散X射线微分析。溶酶体具有最高的铜X射线强度，但溶酶体铜含量与生化指标之间未显示相关性。铜含量的细胞核/无溶酶体细胞质比值与血清转氨酶水平相关。这些结果表明，从无溶酶体细胞质到细胞核的铜增加梯度与肝细胞坏死相关，并且可能导致不可逆的核损伤。
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