Cracowski Jean-Luc, Carpentier Patrick H, Imbert Bernard, Cachot Sandrine, Stanke-Labesque Françoise, Bessard Janine, Bessard Germain
Grenoble University Hospital, Grenoble, France.
Arthritis Rheum. 2002 May;46(5):1319-23. doi: 10.1002/art.10261.
F2-isoprostanes are free radical-dependent arachidonic acid metabolites that are used as clinical markers of lipid peroxidation in systemic sclerosis (SSc) and other microvascular diseases. The objectives of this study were to determine whether the basal urinary levels of F2-isoprostane in SSc patients differ from those in patients with primary Raynaud's phenomenon (RP) and to investigate whether F2-isoprostane formation correlates with the cutaneous microvascular perfusion decrease following cold exposure in SSc patients, patients with primary RP, and healthy controls.
Eleven women with RP secondary to SSc, 11 women with primary RP, and 11 healthy women were exposed to decreasing room temperature, from 25 degrees C to 15 degrees C, for 40 minutes. Urine samples were obtained before and after the test for gas chromatography/electronic impact mass spectrometry quantification of 15-F(2t)-isoprostane (15-F(2t)-IsoP; also called isoprostaglandin F(2alpha) type III). Cutaneous blood flow was monitored using a laser Doppler perfusion imager.
The mean +/- SEM urinary 15-F(2t)-IsoP levels at baseline in SSc patients (178 +/- 32 pmoles/mmole of creatinine) were 1.9 times higher than those in healthy controls (95 +/- 11 pmoles/mmole of creatinine) and 1.7 times higher than those in patients with primary RP (107 +/- 19 pmoles/mmole of creatinine) (P < 0.05 for controls and patients with primary RP versus SSc patients). No significant correlation was found between basal urinary 15-F(2t)-IsoP levels and the temperature or cutaneous blood flow decrease in response to the whole-body cooling. Furthermore, the 15-F(2t)-IsoP response to the cooling test was not correlated with the cutaneous blood flow decrease.
Lipid peroxidation is increased in SSc patients, but not in patients with primary RP. Cold exposure leads to a significant but small increase in 15-F(2t)-IsoP levels that is independent of the cutaneous blood flow decrease. F2-isoprostane quantification may be an interesting pharmacologic tool for monitoring responses to antioxidant treatment in SSc patients.
F2 -异前列腺素是自由基依赖性花生四烯酸代谢产物，用作系统性硬化症（SSc）及其他微血管疾病中脂质过氧化的临床标志物。本研究的目的是确定SSc患者尿中F2 -异前列腺素的基础水平是否与原发性雷诺现象（RP）患者不同，并研究在SSc患者、原发性RP患者和健康对照中，F2 -异前列腺素的生成是否与冷暴露后皮肤微血管灌注减少相关。
11名继发于SSc的RP女性患者、11名原发性RP女性患者和11名健康女性暴露于从25℃降至15℃的室温环境中40分钟。在测试前后采集尿液样本，用于通过气相色谱/电子轰击质谱法定量15 - F(2t)-异前列腺素（15 - F(2t)-IsoP；也称为前列腺素F(2α) III型）。使用激光多普勒灌注成像仪监测皮肤血流。
SSc患者基线时尿中15 - F(2t)-IsoP的平均±标准误水平（178±32皮摩尔/毫摩尔肌酐）比健康对照（95±11皮摩尔/毫摩尔肌酐）高1.9倍，比原发性RP患者（107±19皮摩尔/毫摩尔肌酐）高1.7倍（与SSc患者相比，对照组和原发性RP患者P<0.05）。基础尿15 - F(2t)-IsoP水平与全身冷却后的温度或皮肤血流减少之间未发现显著相关性。此外，冷却试验中15 - F(2t)-IsoP的反应与皮肤血流减少无关。
SSc患者脂质过氧化增加，但原发性RP患者未增加。冷暴露导致15 - F(2t)-IsoP水平显著但小幅升高，这与皮肤血流减少无关。F2 -异前列腺素定量可能是监测SSc患者对抗氧化治疗反应的一种有趣的药理学工具。
