Schivo Michael, Aksenov Alexander A, Pasamontes Alberto, Cumeras Raquel, Weisker Sandra, Oberbauer Anita M, Davis Cristina E
Department of Internal Medicine, Division of Pulmonary and Critical Care Medicine, University of California, Davis, Sacramento, CA 95617, USA. Center for Comparative Respiratory Biology and Medicine, University of California, Davis, Davis, CA 95616, USA.
J Breath Res. 2017 Jan 9;11(1):016007. doi: 10.1088/1752-7163/aa51d7.
Human skin presents a large, easily accessible matrix that is potentially useful for diagnostic applications based on whole body metabolite changes-some of which will be volatile and detected using minimally invasive tools. Unfortunately, identifying skin biomarkers that can be reliably linked to a particular condition is challenging due to a large variability of genetics, dietary intake, and environmental exposures within human populations. This leads to a paucity of clinically validated volatile skin biomarker compounds. Animal models present a very convenient and attractive way to circumvent many of the variability issues. The rabbit (Leporidae) is a potentially logistically useful model to study the skin metabolome, but very limited knowledge of its skin metabolites exists. Here we present the first comprehensive assessment of the volatile fraction of rabbit skin metabolites using polydimethylsiloxane sorbent patch sampling in conjunction with gas chromatography/mass spectrometry. A collection of compounds that are secreted from rabbit skin was documented, and predominantly acyclic long-chain alkyls and alcohols were detected. We then utilized this animal model to study differences between intact skin and skin with early pressure ulcers, as the latter are a major problem in intensive care units. Four New Zealand female white rabbits underwent ulcer formation on one ear with the other ear as a control. Early-stage ulcers were created with neodymium magnets. Histologic analysis showed acute heterophilic dermatitis, edema, and micro-hemorrhage on the ulcerated ears with normal findings on the control ears. The metabolomic analysis revealed subtle but noticeable differences, with several compounds associated with the oxidative stress-related degradation of lipids found to be present in greater abundances in ulcerated ears. The metabolomic findings correlate with histologic evidence of early-stage ulcers. We postulate that the Leporidae model recapitulated the vascular changes associated with ulcer formation. This study illustrates the potential usefulness of the Leporidae model for skin metabolome studies. Additionally, skin metabolome analysis may enhance an understanding of non-skin sources such as urine or breath.
人类皮肤是一个庞大且易于获取的基质，基于全身代谢物变化，它在诊断应用中具有潜在价值——其中一些代谢物是挥发性的，可使用微创工具进行检测。不幸的是，由于人群中基因、饮食摄入和环境暴露存在很大差异，识别能够可靠地与特定病症相关联的皮肤生物标志物具有挑战性。这导致临床上经过验证的挥发性皮肤生物标志物化合物匮乏。动物模型是规避许多变异性问题的非常方便且有吸引力的方法。兔子（兔科）是研究皮肤代谢组在后勤方面可能很有用的模型，但关于其皮肤代谢物的知识非常有限。在此，我们首次使用聚二甲基硅氧烷吸附剂贴片采样结合气相色谱/质谱法，对兔子皮肤代谢物的挥发性成分进行了全面评估。记录了从兔子皮肤分泌的一系列化合物，主要检测到的是无环长链烷基和醇类。然后，我们利用这个动物模型研究完整皮肤与早期压疮皮肤之间的差异，因为后者是重症监护病房中的一个主要问题。四只新西兰雌性白兔，一只耳朵形成溃疡，另一只耳朵作为对照。用钕磁铁造成早期溃疡。组织学分析显示，溃疡耳朵出现急性嗜异性皮炎、水肿和微出血，对照耳朵则无异常发现。代谢组学分析揭示了细微但明显的差异，发现与脂质氧化应激相关降解有关的几种化合物在溃疡耳朵中的含量更高。代谢组学研究结果与早期溃疡的组织学证据相关。我们推测兔科模型概括了与溃疡形成相关的血管变化。本研究说明了兔科模型在皮肤代谢组研究中的潜在用途。此外，皮肤代谢组分析可能会增进对尿液或呼吸等非皮肤来源的理解。
