Volpe A, Biasi D, Caramaschi P, Mantovani W, Bambara L M, Canestrini S, Ferrari M, Poli G, Degan M, Carletto A, Pieropan S, Minuz P
Dipartimento di Medicina Clinica e Sperimentale, Universita di Verona,Verona, Italy.
Rheumatology (Oxford). 2006 Mar;45(3):314-20. doi: 10.1093/rheumatology/kei151. Epub 2005 Oct 11.
Oxidative stress may be one of the important complex pathogenetic mechanisms that lead to damage in scleroderma; free radicals may provoke endothelial injury, fibroblast proliferation and fragmentation of autoantigens favouring induction of autoantibodies. The present study investigates the oxidant status in scleroderma patients by measuring the urinary concentration of 8-isoprostaglandin-F2alpha, an F2-isoprostane, and a product of free radical-mediated peroxidation of arachidonic acid.
Forty-three scleroderma patients (42 women and 1 man, mean age 54.1 yr, mean disease duration 9.0 yr) underwent clinical evaluation and instrumental investigations in order to assess skin, vascular, lung and heart involvement. Von Willebrand factor was evaluated as marker of vascular dysfunction in 36 out of the 43 cases. The urinary level of 8-isoprostaglandin-F2alpha was measured in all scleroderma patients and in the 43 age- and sex-matched healthy controls.
Urinary levels of 8-isoprostaglandin-F2alpha were higher in scleroderma patients than in the healthy control group (341.7 vs 147.6 pg/mg creatinine; P < 0.001). Values of 8-isoprostaglandin-F2alpha were strongly correlated with the nailfold videocapillaroscopy pattern and lung involvement (P = 0.002 and 0.003, respectively), showing increasing levels with the progression of pulmonary severity. Correlation between 8-isoprostaglandin-F2alpha level and von Willebrand factor narrowly failed to reach statistical significance (P = 0.05). There was no correlation between 8-isoprostaglandin-F2alpha concentration and disease activity, vascular, skin and heart involvement, disease pattern or autoantibody profile.
Our study further supports the role of oxidant stress in the pathogenesis of scleroderma, showing a strong correlation between a marker of free radical damage with both the severity of lung involvement and the videocapillaroscopic patterns.
氧化应激可能是导致硬皮病损伤的重要复杂发病机制之一；自由基可能引发内皮损伤、成纤维细胞增殖以及自身抗原片段化，从而促进自身抗体的诱导产生。本研究通过测量8-异前列腺素-F2α（一种F2-异前列腺素，为花生四烯酸自由基介导的过氧化产物）的尿浓度，来研究硬皮病患者的氧化状态。
43例硬皮病患者（42名女性和1名男性，平均年龄54.1岁，平均病程9.0年）接受了临床评估和仪器检查，以评估皮肤、血管、肺和心脏受累情况。在43例患者中的36例中，评估血管性血友病因子作为血管功能障碍的标志物。测量了所有硬皮病患者以及43名年龄和性别匹配的健康对照者的尿8-异前列腺素-F2α水平。
硬皮病患者的尿8-异前列腺素-F2α水平高于健康对照组（341.7对147.6 pg/mg肌酐；P<0.001）。8-异前列腺素-F2α值与甲襞微血管镜检查模式和肺部受累情况密切相关（分别为P = 0.002和0.003），随着肺部严重程度的进展，水平升高。8-异前列腺素-F2α水平与血管性血友病因子之间的相关性勉强未达到统计学显著性（P = 0.05）。8-异前列腺素-F2α浓度与疾病活动度、血管、皮肤和心脏受累情况、疾病模式或自身抗体谱之间均无相关性。
我们的研究进一步支持氧化应激在硬皮病发病机制中的作用，显示自由基损伤标志物与肺部受累严重程度和微血管镜检查模式之间存在密切相关性。
