Gouveia-Figueira Sandra, Nording Malin L, Gaida Jamie E, Forsgren Sture, Alfredson Håkan, Fowler Christopher J
Department of Pharmacology and Clinical Neuroscience, Pharmacology Unit, Umeå University, Umeå, Sweden; Department of Chemistry, Umeå University, Umeå, Sweden.
Department of Chemistry, Umeå University, Umeå, Sweden.
PLoS One. 2015 Apr 13;10(4):e0123114. doi: 10.1371/journal.pone.0123114. eCollection 2015.
Linoleic acid-derived oxidation products are found in experimental pain models. However, little is known about the levels of such oxylipins in human pain. In consequence, in the present study, we have undertaken a lipidomic profiling of oxylipins in blood serum from patients with Achilles tendinopathy and controls.
METHODOLOGY/PRINCIPAL FINDINGS: A total of 34 oxylipins were analysed in the serum samples. At a significance level of P<0.00147 (<0.05/34), two linoleic acid-derived oxylipins, 13-hydroxy-10E,12Z-octadecadienoic (13-HODE) and 12(13)-dihydroxy-9Z-octadecenoic acid (12,13-DiHOME) were present at significantly higher levels in the Achilles tendinopathy samples. This difference remained significant when the dataset was controlled for age, gender and body-mass index. In contrast, 0/21 of the arachidonic acid- and 0/4 of the dihomo-γ-linolenic acid, eicosapentaenoic acid or docosahenaenoic acid-derived oxylipins were higher in the patient samples at this level of significance. The area under the Receiver-Operator Characteristic (ROC) curve for 12,13-DiHOME was 0.91 (P<0.0001). Levels of four N-acylethanolamines were also analysed and found not to be significantly different between the controls and the patients at the level of P<0.0125 (<0.05/4).
CONCLUSIONS/SIGNIFICANCE: It is concluded from this exploratory study that abnormal levels of linoleic acid-derived oxylipins are seen in blood serum from patients with Achilles tendinopathy. Given the ability of two of these, 9- and 13-HODE to activate transient receptor potential vanilloid 1, it is possible that these changes may contribute to the symptoms seen in Achilles tendinopathy.
亚油酸衍生的氧化产物在实验性疼痛模型中被发现。然而，关于此类氧化脂质在人类疼痛中的水平知之甚少。因此，在本研究中，我们对跟腱病患者和对照组血清中的氧化脂质进行了脂质组学分析。
方法/主要发现：在血清样本中总共分析了34种氧化脂质。在显著性水平P<0.00147（<0.05/34）时，两种亚油酸衍生的氧化脂质，13-羟基-10E,12Z-十八碳二烯酸（13-HODE）和12(13)-二羟基-9Z-十八碳烯酸（12,13-DiHOME）在跟腱病样本中的水平显著更高。当对数据集进行年龄、性别和体重指数控制时，这种差异仍然显著。相比之下，在该显著性水平下，花生四烯酸衍生的氧化脂质中0/21以及二高-γ-亚麻酸、二十碳五烯酸或二十二碳六烯酸衍生的氧化脂质中0/4在患者样本中更高。12,13-DiHOME的受试者工作特征（ROC）曲线下面积为0.91（P<0.0001）。还分析了四种N-酰基乙醇胺的水平，发现在P<0.0125（<0.05/4）水平下，对照组和患者之间没有显著差异。
结论/意义：从这项探索性研究得出的结论是，跟腱病患者血清中亚油酸衍生的氧化脂质水平异常。鉴于其中两种，9-和13-HODE能够激活瞬时受体电位香草酸亚型1，这些变化可能导致跟腱病中出现的症状。
