Sternlieb I, Quintana N, Volenberg I, Schilsky M L
National Center for the Study of Wilson's Disease, St. Luke's/Roosevelt Medical Center-Columbia University, New York, NY 10019, USA.
Hepatology. 1995 Dec;22(6):1782-7.
In an attempt to identify the cellular targets of copper toxicity, we studied the ultrastructure of hepatocytes in the livers of 23 Long-Evans Cinnamon (LEC) rats ranging in age from 10 to 89 weeks. The hepatic copper concentration ranged from 325 to 2,126 (mean, 930) micrograms/g dry weight. Thirteen rats displayed varying degrees of jaundice at the time of killing. Numerous nuclei were indented by cytoplasmic invaginations. Conspicuous abnormalities were displayed by mitochondria. These included marked pleomorphism; increased or diminished matrical density; rearrangement, elongation, dilatation, stacking, or disappearance of cristae; absence of matrical granules; presence of matrical inclusions of flocculent electron-dense deposits; and degenerative changes. The severity of the ultrastructural changes did not correlate with the hepatic copper concentration but did correlate with the degree of the icterus displayed by the rats. Certain mitochondrial changes resembled those encountered in the hepatocytes of patients with Wilson's disease, confirming that these organelles are important targets of copper toxicity.
为了确定铜毒性的细胞靶点，我们研究了23只年龄在10至89周之间的长 Evans 肉桂色（LEC）大鼠肝脏中肝细胞的超微结构。肝脏铜浓度范围为325至2126（平均930）微克/克干重。13只大鼠在处死时表现出不同程度的黄疸。许多细胞核被细胞质内陷压出凹痕。线粒体呈现出明显异常。这些异常包括显著的多形性；基质密度增加或减少；嵴的重排、伸长、扩张、堆叠或消失；基质颗粒缺失；存在絮状电子致密沉积物的基质内含物；以及退行性变化。超微结构变化的严重程度与肝脏铜浓度无关，但与大鼠表现出的黄疸程度相关。某些线粒体变化类似于威尔逊病患者肝细胞中所见到的变化，证实这些细胞器是铜毒性的重要靶点。
