F2-异前列腺素8-表前列腺素F2α可增加血小板黏附，并降低一氧化氮的抗黏附和抗聚集作用。

The F2-isoprostane 8-epiprostaglandin F2alpha increases platelet adhesion and reduces the antiadhesive and antiaggregatory effects of NO.

作者信息

Minuz P, Andrioli G, Degan M, Gaino S, Ortolani R, Tommasoli R, Zuliani V, Lechi A, Lechi C

机构信息

Institute of Clinica Medica, University of Verona, Italy.

出版信息

Arterioscler Thromb Vasc Biol. 1998 Aug;18(8):1248-56. doi: 10.1161/01.atv.18.8.1248.

DOI:10.1161/01.atv.18.8.1248

PMID:9714131

Abstract

F2-isoprostanes are prostaglandin (PG) isomers produced in vivo through free radical-catalyzed peroxidation of arachidonic acid, which may affect platelet function. The current study investigated the effects of 8-epiprostaglandin F2alpha (8-epi-PGF2alpha) on critical events of platelet activation. A dose-dependent increase in platelet adhesion to fibrinogen- and plasma-coated microwells by 8-epi-PGF2alpha (1 to 1000 nmol/L) was observed when resting platelets (plasma from 1.3+/-0.2% to 5.5+/-0.2%, EC50 of 48 nmol/L; fibrinogen from 3.3+/-0.3% to 6.4+/-0.2%, EC50 of 35 nmol/L; mean+/-SEM, n=8, P<0.001) and thrombin-stimulated human platelets were used. The expression of the adhesion molecule glycoprotein IIb/IIIa was increased by 10 to 1000 nmol/L 8-epi-PGF2alpha in resting platelets (from 64.8+/-2.1% to 83.9+/-1.3%; n=5, P<0.01) and in stimulated platelets. The secretion of the glycoprotein GMP-140 increased only in the presence of both thrombin and 10 to 1000 nmol/L 8-epi-PGF2alpha (from 48.5+/-3.1% to 63.1+/-2.0%, P<0.05). The antiaggregatory effects of both the NO donor NOR-3 (basal, 21.4+/-4.6%; with 8-epi-PGF2alpha, 30.8+/-6.9%; n=14, P<0.05) and endothelial cells that release NO (basal, 18.5+/-4.6%; with 8-epi-PGF2alpha, 30.7+/-5.3%; n=15, P<0.001) were also reduced. All of these effects were prevented by the thromboxane receptor antagonist GR32191 but not affected by acetylsalicylic acid. An increase in free intracellular calcium concentration, measured with the use of fura 2, was observed with 8-epi-PGF2alpha. In conclusion, F2-isoprostanes may participate in oxidative injury by inducing platelet activation and by reducing the antiplatelet activity of NO: increased platelet adhesiveness and expression of the fibrinogen receptor are induced by nanomolar amounts of 8-epi-PG-F2alpha. Platelet secretion and aggregation can also be induced in the presence of platelet agonists.

摘要

F2 - 异前列腺素是体内通过自由基催化花生四烯酸过氧化产生的前列腺素（PG）异构体，可能会影响血小板功能。本研究调查了8 - 表前列腺素F2α（8 - epi - PGF2α）对血小板活化关键事件的影响。当使用静息血小板（血浆从1.3±0.2%增至5.5±0.2%，半数有效浓度为48 nmol/L；纤维蛋白原从3.3±0.3%增至6.4±0.2%，半数有效浓度为35 nmol/L；均值±标准误，n = 8，P < 0.001）和凝血酶刺激的人血小板时，观察到8 - epi - PGF2α（1至1000 nmol/L）使血小板对纤维蛋白原和血浆包被微孔的黏附呈剂量依赖性增加。在静息血小板（从64.8±2.1%增至83.9±1.3%；n = 5，P < 0.01）和刺激的血小板中，10至1000 nmol/L的8 - epi - PGF2α使黏附分子糖蛋白IIb/IIIa的表达增加。仅在凝血酶和10至1000 nmol/L的8 - epi - PGF2α同时存在时，糖蛋白GMP - 140的分泌增加（从48.5±3.1%增至63.1±2.0%，P < 0.05）。一氧化氮供体NOR - 3（基础值，21.4±4.6%；与8 - epi - PGF2α共同作用时，30.8±6.9%；n = 14，P < 0.05）和释放一氧化氮的内皮细胞（基础值，18.5±4.6%；与8 - epi - PGF2α共同作用时，30.7±5.3%；n = 15，P < 0.001）的抗聚集作用也降低。所有这些作用均被血栓素受体拮抗剂GR32191阻断，但不受乙酰水杨酸影响。使用fura 2测量发现，8 - epi - PGF2α可使细胞内游离钙浓度升高。总之，F2 - 异前列腺素可能通过诱导血小板活化和降低一氧化氮的抗血小板活性参与氧化损伤：纳摩尔量的8 - epi - PG - F2α可诱导血小板黏附性增加和纤维蛋白原受体表达增加。在血小板激动剂存在的情况下，也可诱导血小板分泌和聚集。