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飞行时间二次离子质谱分析人类肺组织揭示 COPD(GOLD IV)患者铁沉积增加。

ToF-SIMS mediated analysis of human lung tissue reveals increased iron deposition in COPD (GOLD IV) patients.

机构信息

Medicinal Chemistry, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

Target & Translational Science, Respiratory, Inflammation and Autoimmunity, IMED Biotech Unit, AstraZeneca, Gothenburg, Sweden.

出版信息

Sci Rep. 2019 Jul 11;9(1):10060. doi: 10.1038/s41598-019-46471-7.

Abstract

Chronic obstructive pulmonary disease (COPD) is a debilitating lung disease that is currently the third leading cause of death worldwide. Recent reports have indicated that dysfunctional iron handling in the lungs of COPD patients may be one contributing factor. However, a number of these studies have been limited to the qualitative assessment of iron levels through histochemical staining or to the expression levels of iron-carrier proteins in cells or bronchoalveolar lavage fluid. In this study, we have used time of flight secondary ion mass spectrometry (ToF-SIMS) to visualize and relatively quantify iron accumulation in lung tissue sections of healthy donors versus severe COPD patients. An IONTOF 5 instrument was used to perform the analysis, and further multivariate analysis was used to analyze the data. An orthogonal partial least squares discriminant analysis (OPLS-DA) score plot revealed good separation between the two groups. This separation was primarily attributed to differences in iron content, as well as differences in other chemical signals possibly associated with lipid species. Further, relative quantitative analysis revealed twelve times higher iron levels in lung tissue sections of COPD patients when compared to healthy donors. In addition, iron accumulation observed within the cells was heterogeneously distributed, indicating cellular compartmentalization.

摘要

慢性阻塞性肺疾病(COPD)是一种使人虚弱的肺部疾病,目前是全球第三大致死原因。最近的报告表明,COPD 患者肺部铁代谢功能障碍可能是一个促成因素。然而,许多此类研究仅限于通过组织化学染色对铁水平进行定性评估,或对细胞或支气管肺泡灌洗液中铁载体蛋白的表达水平进行评估。在这项研究中,我们使用飞行时间二次离子质谱(ToF-SIMS)来可视化和相对定量健康供体与严重 COPD 患者的肺组织切片中的铁积累。IONTOF 5 仪器用于进行分析,并进一步使用多元分析来分析数据。正交偏最小二乘判别分析(OPLS-DA)得分图显示两组之间的良好分离。这种分离主要归因于铁含量的差异,以及可能与脂质种类相关的其他化学信号的差异。此外,相对定量分析显示,与健康供体相比,COPD 患者的肺组织切片中铁水平高 12 倍。此外,观察到细胞内的铁积累呈不均匀分布,表明细胞区室化。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/d5f2/6624371/d2dc4b97d7c4/41598_2019_46471_Fig1_HTML.jpg

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