Medizinische Universität Wien, Univ. Klinik für Innere Medizin II, Institut für Arbeitsmedizin, Austria.
Deutsches Elektronen-Synchrotron (DESY), Photon Science, Germany.
J Trace Elem Med Biol. 2019 Jan;51:42-49. doi: 10.1016/j.jtemb.2018.09.007. Epub 2018 Sep 27.
of this investigation were to quantify copper (Cu), iron (Fe) and zinc (Zn) along with sulphur (S) and phosphorus (P) in hepatocytes and connective tissue in liver section from patients with Wilson´s disease (WD) by micro Synchrotron X-ray fluorescence (μ-SRXRF). Secondly to establish two-dimensional μ-SRXRF element mappings for comparison with histologically prepared slices, and thirdly to assess whether elemental distributions are associated.
Archival liver tissues from twelve patients with end-stage cirrhosis or fulminant WD were investigated. Mutations in ATP7B have been classified before. For control seven archived normal liver tissues were investigated. μ-SRXRF measurements were performed at the DORIS III storage ring at HASYLAB/DESY (Hamburg, Germany). Two-dimensional element distribution were compared with histologically prepared slices about 20-30 μm apart from those investigated by μ-SRXRF.
Elementary copper (Cu) could be demonstrated in all investigated liver sections simultaneously with Fe, Zn, P and S. In WD mean Cu was 20 fold increased in hepatocytes and threefold in fibrotic areas in comparison with controls. In regeneration nodules Cu was strikingly inhomogeneous distributed. Cu concentrations measured by μ-SRXRF correlated with those measured by atom absorption spectroscopy. Strong associations in their regional distribution existed between Zn and Cu or Fe and S. Moreover, differences in Cu/S were found between hepatocytes and fibrotic areas. An increase of Fe could only be documented in hepatocytes compared to fibrotic areas. With a beam size of 15 x 15 μm two-dimensional distributions of these elements are morphologically comparable with histological section with a magnification of about 25x optic microscope.
μ-SRXRF investigations are a valuable tool for quantifying element concentrations in biological tissues and further provide 2-dimensional information of element distribution and elemental association in a biological tissues, thus speeding up basic knowledge in a synopsis with biological and clinical data.
本研究旨在通过微同步辐射 X 射线荧光（μ-SRXRF）定量测定威尔逊病（WD）患者肝组织切片中肝细胞和结缔组织中的铜（Cu）、铁（Fe）、锌（Zn）以及硫（S）和磷（P）。其次，建立二维μ-SRXRF 元素图谱，与组织学切片进行比较，第三，评估元素分布是否相关。
研究了 12 例终末期肝硬化或暴发性 WD 患者的存档肝组织。ATP7B 基因突变已在此前进行了分类。为了对照，还研究了 7 例存档的正常肝组织。μ-SRXRF 测量在德国汉堡 HASYLAB/DESY 的 DORIS III 储存环上进行。二维元素分布与距 μ-SRXRF 研究的组织学切片相差约 20-30μm 的切片进行比较。
在所有研究的肝切片中，都可以同时显示基本的铜（Cu）、Fe、Zn、P 和 S。与对照组相比，WD 患者的肝细胞和纤维化区域中的 Cu 分别增加了 20 倍和 3 倍。在再生结节中，Cu 的分布明显不均匀。通过 μ-SRXRF 测量的 Cu 浓度与原子吸收光谱法测量的浓度相关。Zn 和 Cu 或 Fe 和 S 的区域分布之间存在很强的相关性。此外，在肝细胞和纤维化区域之间发现了 Cu/S 的差异。与纤维化区域相比，仅在肝细胞中检测到 Fe 的增加。使用 15×15μm 的光束尺寸，这些元素的二维分布在形态上与放大倍数约为 25x 光学显微镜的组织学切片相当。
μ-SRXRF 研究是定量测定生物组织中元素浓度的有效工具，进一步提供了生物组织中元素分布和元素相关性的二维信息，从而加速了生物学和临床数据综合的基础知识。
