兔内源性白三烯B4和E4产化趋化肽FMLP的动力学研究

Antonio Celardo , Giuseppe Dell’Elba , Stefano Manarini , Virgilio Evangelista , Giovanni de Gaetano , Chiara Cerletti
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引用次数: 4

摘要

用30 nmol/kg静脉注射炎性肽n -甲酰基-甲硫基-l-亮基-l-苯丙氨酸(FMLP)后,观察白三烯B4 (LTB4)和E4 (LTE4)在雄性家兔体内的动力学变化。LTB4和LTE4浓度分别在2 min和5 min达到最大值,分别为84.2±60.0和162.2±51.4 nmol/L(平均±s.d)。FMLP给药后,LTB4和LTE4的第一个消除期的表观半衰期分别为24.6±6.7 min和36.9±13.0 min。LTB4和LTE4血药浓度-时间曲线下面积(AUC, nmol min/L)分别为2178±1591和7627±3052。LTE4和N-ac-LTE4是尿中排泄的主要成分,主要在FMLP治疗后收集尿的第一时间间隔(0-12 h)排出;11-反式lte4在第二次间歇(12-24 h)被回收。另外两种极性化合物(潜在代谢物)在第一次尿液收集期间被回收。内源性产生的白三烯的动力学特性的知识可能有助于理解这些类二十烷在炎症和血栓性疾病中的作用,以及评估旨在调节其产生和作用的药物的功效。
本文章由计算机程序翻译,如有差异,请以英文原文为准。
Kinetics of Endogenous Leukotriene B4 and E4 Production Following Injection of the Chemotactic Peptide FMLP in the Rabbit

The kinetic profiles of leukotriene B4 (LTB4) and E4 (LTE4) after intravenous administration (30 nmol/kg) of the inflammatory peptide N-formyl-l-methionyl-l-leucyl-l-phenylalanine (FMLP) were evaluated in male rabbits. LTB4 and LTE4 reached the maximal concentration of 84.2 ± 60.0 and 162.2 ± 51.4 nmol/L (mean ± s.d.), at 2 and 5 min, respectively. The first elimination phase for LTB4 and LTE4, after FMLP administration, showed an apparent half-life of 24.6 ± 6.7 and 36.9 ± 13.0 min, respectively. The area under the blood concentration-time curve (AUC, nmol min/L) of LTB4 and LTE4 was 2178 ± 1591 and 7627 ± 3052, respectively. LTE4 and N-ac-LTE4 were the major components excreted in the urine, mostly in the first time interval (0–12 h) of urinary collection after FMLP treatment; 11-trans-LTE4 was recovered in the second interval (12–24 h). Two other more polar compounds, potential metabolites, were recovered in the first interval of urine collection. Knowledge of the kinetic characteristics of endogenously produced leukotrienes may be useful in understanding the role of these eicosanoids in inflammatory and thrombotic disease, as well as in evaluating the efficacy of drugs designed to modulate their production and effect.

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