Suzuki N, Hishinuma T, Abe F, Omata K, Ito S, Sugiyama M, Mizugaki M
Department of Pharmaceutical Sciences, Tohoku University Hospital, Sendai, Japan.
Prostaglandins Other Lipid Mediat. 2000 Oct;62(4):395-403. doi: 10.1016/s0090-6980(00)00091-5.
Bronchoconstrictor cysteinyl leukotrienes (LT) and thromboxane (TX) A2 have been implicated in the pathogenesis of asthma. Determination of urinary leukotriene E4 (LTE4) and 11-dehydro-TXB2 levels are often used to assess cysteinyl LT and TXA2 production in humans. To define the potential role in the pathogenesis of asthma, we investigated the urinary LTE4 and 11-dehydro-TXB2 levels. LTE4 and 11-dehydro-TXB2 levels were determined using liquid chromatography/tandem mass spectrometry (LC/MS) and gas chromatography/mass spectrometry (GC/MS), respectively. Urinary LTE4 levels in asthmatic patients (192 +/- 122 pg/mg creatinine, n = 14) were significantly higher (P < 0.005) than those in healthy volunteers (55 +/- 16 pg/mg creatinine, n = 13), but no significant difference in 11-dehydro-TXB2 levels was observed. A significant inverse correlation (r = -0.821, P < 0.005) was found between urinary LTE4 levels and the forced expiratory volume in 1 s (FEV1) but no significant correlation was observed between urinary 11-dehydro-TXB2 levels and FEV1. The present findings suggest that cysteinyl LTs play a more important role in the pathogenesis of asthma than TXA2.
支气管收缩性半胱氨酰白三烯(LT)和血栓素(TX)A2与哮喘的发病机制有关。测定尿白三烯E4(LTE4)和11-脱氢-TXB2水平常用于评估人类半胱氨酰LT和TXA2的产生。为了确定其在哮喘发病机制中的潜在作用,我们研究了尿LTE4和11-脱氢-TXB2水平。分别使用液相色谱/串联质谱(LC/MS)和气相色谱/质谱(GC/MS)测定LTE4和11-脱氢-TXB2水平。哮喘患者的尿LTE4水平(192±122 pg/mg肌酐,n = 14)显著高于健康志愿者(55±16 pg/mg肌酐,n = 13)(P < 0.005),但11-脱氢-TXB2水平未观察到显著差异。尿LTE4水平与第1秒用力呼气量(FEV1)之间存在显著负相关(r = -0.821,P < 0.005),但尿11-脱氢-TXB2水平与FEV1之间未观察到显著相关性。目前的研究结果表明,半胱氨酰LT在哮喘发病机制中比TXA2起更重要的作用。