Loï C, Chardigny J M, Berdeaux O, Vatèle J M, Poullain D, Noël J P, Sébédio J L
INRA, Unité de Nutrition Lipidique, Dijon, France.
Thromb Haemost. 1998 Oct;80(4):656-61.
Three trans isomers of eicosapentaenoic acid (EPA) were added to rat platelets stimulated with arachidonic acid (AA) in order to compare their effects on platelet aggregation and on AA oxygenation with those of EPA. The production of metabolites from radiolabelled 20:5delta 17trans was studied also. EPA induced an inhibition of platelet aggregation of 26.7 +/- 6.6% for a 20:5/20:4 ratio equal to 1. The 20:5delta 11trans and the 20:5delta 11trans,17trans were twice as antiaggregant. In contrast, the 20:5delta 17trans induced similar antiaggregant effect as its cis homologue. Each fatty acid showed a dose-dependent effect. In opposition to EPA, 20:5delta 17trans was also able to induce platelet aggregation (12 +/- 4.9% at 5 microM). With regards to the metabolism of AA, 20:5delta 11trans, 20:5delta 17trans and 20:5delta 11trans,17trans (20:5/20:4 = 1) reduced the formation of the cyclooxygenase metabolites (-63%, -37% and -68%, respectively) and enhanced that of 12-HETE (+67%, +38% and +74%, respectively) as compared to EPA. The analysis showed that radiolabelled 20:5delta 17trans was metabolized into five compounds which remained to be identified. The Rf of three of these compounds (X1, X2 and X4) were those of the metabolites of EPA. Experiments using baicalein induced an inhibition of the production of X2. This suggested that this compound was formed through the 12-lipoxygenase pathway. In the same way, using indomethacin as inhibitor, we observed that X1 and X4 were produced by the cyclooxygenase pathway. Our results suggest that the trans double bond in the delta 11 position may be responsible of the different physiological effects of the trans polyunsaturated fatty acids as compared to their cis homologue (EPA). Furthermore, 20:5delta 17trans seems to be recognised by the enzymatic system as 20:4 n-6.
将二十碳五烯酸（EPA）的三种反式异构体添加到用花生四烯酸（AA）刺激的大鼠血小板中，以比较它们对血小板聚集以及对AA氧化的影响与EPA的影响。还研究了放射性标记的20:5δ17反式代谢产物的产生。对于20:5/20:4比率等于1的情况，EPA诱导血小板聚集抑制26.7±6.6%。20:5δ11反式和20:5δ11反式，17反式的抗聚集作用是其两倍。相比之下，20:5δ17反式诱导的抗聚集作用与其顺式同系物相似。每种脂肪酸都显示出剂量依赖性效应。与EPA相反，20:5δ17反式也能够诱导血小板聚集（在5 microM时为12±4.9%）。关于AA的代谢，与EPA相比，20:5δ11反式、20:5δ17反式和20:5δ11反式，17反式（20:5/20:4 = 1）减少了环氧化酶代谢产物的形成（分别为-63%、-37%和-68%），并增加了12-HETE的形成（分别为+67%、+38%和+74%）。分析表明，放射性标记的20:5δ17反式代谢为五种化合物，其身份尚待确定。其中三种化合物（X1、X2和X4）的Rf与EPA的代谢产物相同。使用黄芩素的实验诱导了X2产生的抑制。这表明该化合物是通过12-脂氧合酶途径形成的。同样，使用吲哚美辛作为抑制剂，我们观察到X1和X4是由环氧化酶途径产生的。我们的结果表明，与它们的顺式同系物（EPA）相比，δ11位的反式双键可能是反式多不饱和脂肪酸不同生理效应的原因。此外，20:5δ17反式似乎被酶系统识别为20:4 n-6。
