Laser ablation-inductively coupled plasma-mass spectrometry (LA-ICP-MS) was deployed for quantitative mapping of the Cu distribution in cryo-sections of liver tissue from mice with cholestatic liver disease induced via common bile duct ligation (CBDL). Cu distribution maps of the liver sections were obtained from the CBDL-operated mice sacrificed at different time points (2, 4 and 6 weeks) after the surgical intervention and compared with those of the corresponding control (sham-operated) mice. Cu quantification was accomplished versus matrix-matched thin sections of spiked liver tissue homogenates and versus spiked gelatin droplet standards. No statistical differences were obtained between the results using the two calibration approaches and thus, both were considered suitable for quantitative Cu bioimaging of liver cryo-sections. On the basis of practical considerations, i.e. simplicity, low cost and availability of the material, spiked gelatin droplet standards are the preferred choice for quantitative determination of the Cu distribution in liver tissue cryo-sections. An inhomogeneous hepatic Cu distribution was observed in the CBDL mice, in contrast to the homogeneous hepatic Cu distribution established for the sham-operated mice. The Cu levels increased with the progression of the disease and a strong accumulation was observed in some necrotic areas. High-resolution LA-ICP-MS bioimaging, using a circular spot size of 2 μm, was suitable for the visualization of the Cu distribution in liver tissue on a (sub-)cellular level. In addition to the quantitative Cu mapping, the spatial distribution of Zn was also monitored in the liver cryo-sections of the control and the 2, 4 and 6 week CBDL mice, but in all cases, Zn was homogeneously distributed across the tissue.

中文翻译：

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激光消融-电感耦合等离子体质谱法定量绘制胆总管结扎致肝病小鼠肝脏组织切片中铜的分布

激光烧蚀电感耦合等离子体-质谱（LA-ICP-MS）部署在肝组织的冷冻切片在Cu分布从小鼠诱导的胆汁淤积性肝病的定量映射经由胆总管结扎（CBDL）。从手术干预后不同时间点（2、4和6周）处死的CBDL手术小鼠获得肝脏切片的Cu分布图，并将其与相应的对照（假手术）小鼠进行比较。铜定量完成与基质匹配薄的尖刺肝组织匀浆和节与加标明胶滴标准品。使用两种校准方法在结果之间未获得统计差异，因此，两种方法均被认为适用于肝脏冰冻切片的定量Cu生物成像。基于实际考虑，即为简化，低成本和材料的可用性，加标明胶液滴标准液是定量测定肝脏组织冷冻切片中Cu分布的首选。在CBDL小鼠中观察到肝Cu分布不均匀，与为假手术小鼠建立的肝Cu分布相反。铜水平随疾病的进展而增加，并且在一些坏死区域中观察到大量积累。使用2μm圆形斑点的高分辨率LA-ICP-MS生物成像技术适合在（亚）细胞水平上可视化肝组织中的铜分布。除了定量的Cu作图外，还在对照组和第2、4和6周CBDL小鼠的肝脏冰冻切片中监测Zn的空间分布，但在所有情况下，