摘要
【目的】研究不同月龄TX小鼠的铜代谢情况、肝脏功能和病理学损害特点,为以TX鼠为模型的研究在选择不同月龄动物方面提供适合的时间点。【方法】选取1~6月的每月龄TX小鼠和同系DL小鼠雌雄各3只,分别作为病例组和对照组,测定肝、脑、肾、血清中的金属铜含量,测定血清铜蓝蛋白及谷草转氨酶等指标,肝脏标本HE染色观察组织病理学改变,电镜下观察超微结构。【结果】TX小鼠自第2月起肝、脑的干体质量铜含量较对照组明显增高(P<0.05),肝脏增高幅度更甚,至4月龄时两组差异尤为显著,同期肾铜增高及血清铜降低与对照组相比有统计学意义(P<0.05);血清铜蓝蛋白明显降低;转氨酶的升高以第5月时为著;病理改变光镜下主要为变性坏死,胞核空泡样变,电镜下见线粒体、溶酶体中大量电子致密物沉积,以第4月时最重。【结论】理想的Wilson病模型和肝损害动物模型,症状前治疗的探索可选用1月龄的TX鼠,出现临床症状后治疗的探索应选用2月龄小鼠,病情高峰时期的实验可考虑选用4、5月龄的动物。
Objective] To explore the characteristics of copper metabolism and the liver functional and pathological indexes, so to provide right time points in selection of variously aged animals based on the TX mice model. [Methods]One to six month old TX and DL mice were included as the experimental and control group. Each group contained three female and three male mice. The concentration of copper in the serum, dry tissues (liver, brain, and kidney), together with some copper biochemistry indexes were measured. The samples were taken for HE staining and electron microscope study regarding pathological changes. [Results]From the second month, the concentration of copper in liver and brain increased significantly compared to the control group (P< 0.05), especially in liver. The differences became more apparently at the age of four months, at the same time point kidney copper concentration increased and serum copper decreased. The differences were significant compared with those in control group (P< 0.05). At month five, serum ceruloplasmin decreased and transaminase increased dramatically. The pathological change mainly lies in degeneration, necrosis, and vacuoles in nucleus under optical microscope, and large amount of dense electron depositions in lysosomes and mitochondria under electron microscope, which became the severest at month four. [Conclusion]As a suitable model for Wilson disease and secondary liver damage, one-month-old TX mice can be used for the studies before onset of illness. Two-month-old ones can be used for the exploration of treatment after the onset. Four to five months old ones can be used for the peak time of the disease.
出处
《中山大学学报(医学科学版)》
CAS
CSCD
北大核心
2005年第3期253-256,共4页
Journal of Sun Yat-Sen University:Medical Sciences
基金
国家自然科学基金资助项目(3040147)
卫生部重大项目基金资助项目(2001321)
"211工程"重点建设基金资助项目(中山医科大学)
关键词
小鼠
铜
肝豆状核变性
疾病模型
动物
时间因素
mouse
copper
hepatolenticular degeneration
disease model, animal
time factor