通过质谱成像快速识别肾脏组织中的缺血性损伤。,Analytical Chemistry

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通过质谱成像快速识别肾脏组织中的缺血性损伤。
Analytical Chemistry ( IF 6.7 ) Pub Date : 2019-01-31 00:00:00 , DOI: 10.1021/acs.analchem.8b05521
T C van Smaalen ₁ , S R Ellis ₂ , N E Mascini ₂ , T Porta Siegel ₂ , B Cillero-Pastor ₂ , L M Hillen _{3,

4} , L W E van Heurn ₁ , C J Peutz-Kootstra ₃ , R M A Heeren ₂

Affiliation

质谱成像（MSI）的分析速度不断提高，引起了人们对医学领域的浓厚兴趣。急性肾损伤是一种高发病率和高死亡率的严重疾病。没有可靠的临界值可以估计急性肾损伤的严重程度。因此，需要快速而准确地评估急性缺血的新工具，其在重症监护和肾脏移植中具有重要的临床意义。我们调查了MSI在猪模型中评估急性缺血性肾组织的价值。建立了一个灌注模型，其中成对的肾脏接受了温暖（严重）或寒冷（轻微）缺血（n=每组8个）。首先，两名失明的病理学家对缺血性组织损伤进行了系统的评估。其次，对肾脏组织进行MALDI-MSI，以研究脂质在组织中的空间分布和组成。组织病理学检查显示肾脏之间无显着差异，而MALDI-MSI能够通过在2 h内整个组织中特征性脂质降解产物的差异表达来详细区分严重和轻度缺血。特别地，严重缺血后，包括溶血心磷脂，溶血磷脂酰胆碱和溶血磷脂酰肌醇在内的溶血脂显着升高。这项研究证明了MSI在临床可接受的时间范围内分化和鉴定早期缺血性损伤分子模式的巨大潜力。

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Rapid Identification of Ischemic Injury in Renal Tissue by Mass-Spectrometry Imaging.

The increasing analytical speed of mass-spectrometry imaging (MSI) has led to growing interest in the medical field. Acute kidney injury is a severe disease with high morbidity and mortality. No reliable cut-offs are known to estimate the severity of acute kidney injury. Thus, there is a need for new tools to rapidly and accurately assess acute ischemia, which is of clinical importance in intensive care and in kidney transplantation. We investigated the value of MSI to assess acute ischemic kidney tissue in a porcine model. A perfusion model was developed where paired kidneys received warm (severe) or cold (minor) ischemia (n = 8 per group). First, ischemic tissue damage was systematically assessed by two blinded pathologists. Second, MALDI-MSI of kidney tissues was performed to study the spatial distributions and compositions of lipids in the tissues. Histopathological examination revealed no significant difference between kidneys, whereas MALDI-MSI was capable of a detailed discrimination of severe and mild ischemia by differential expression of characteristic lipid-degradation products throughout the tissue within 2 h. In particular, lysolipids, including lysocardiolipins, lysophosphatidylcholines, and lysophosphatidylinositol, were dramatically elevated after severe ischemia. This study demonstrates the significant potential of MSI to differentiate and identify molecular patterns of early ischemic injury in a clinically acceptable time frame. The observed changes highlight the underlying biochemical processes of acute ischemic kidney injury and provide a molecular classification tool that can be deployed in assessment of acute ischemic kidney injury.

更新日期：2019-01-31

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