Akinshola B E, Verma P S, Taylor R E
Howard University College of Medicine, Department of Pharmacology, Washington, D. C. 20059, USA.
Thromb Res. 1995 Aug 15;79(4):343-51. doi: 10.1016/0049-3848(95)00122-8.
The level of cyclic adenosine monophosphate (cAMP) in human platelets is known to be an important regulator of platelet function. The polyunsaturated fatty acids (PUFA) dihomo-gamma-linolenic acid (DHLA), and eicosapentaenoic acid (EPA), precursors of the prostaglandin (PG) 1 and 3 series respectively, were studied for their ability to stimulate platelet cAMP and/or PGE1 levels, and to inhibit platelet aggregation (PAg). Incubation of washed platelets (1 x 10(8)/ml) with 125 microM DHLA increased intraplatelet levels of PGE1 from 197 +/- 7 to 1622 +/- 9.7 picograms/10(8), cAMP from 3 +/- 0.8 to 31 +/- 1.9 picomoles/10(8), and inhibited collagen-induced PAg. Addition of 1 mumole of xanthine per unit of xanthine oxidase (a superoxide radical generating system) to the incubating medium potentiated the effects of both fatty acids, whereas 240 microM Hydrogen Peroxide (H2O2) inhibited these effects. These results suggest that: (1) DHLA may be more effective in inhibiting PAg than EPA, which has been reported to reduce the incidence of coronary diseases in some human populations; (2) That superoxide radical may activate the platelet cyclooxygenase system to increase lipid peroxidation of these PUFA prostanoid precursors and may result in the inhibition of PAg, whereas H2O2 may have an opposite effect.
已知人血小板中环磷酸腺苷（cAMP）水平是血小板功能的重要调节因子。分别研究了前列腺素（PG）1系列和3系列的前体多不饱和脂肪酸（PUFA）二高-γ-亚麻酸（DHLA）和二十碳五烯酸（EPA）刺激血小板cAMP和/或PGE1水平以及抑制血小板聚集（PAg）的能力。将洗涤后的血小板（1×10⁸/ml）与125μM DHLA孵育，可使血小板内PGE1水平从197±7皮克/10⁸升高至1622±9.7皮克/10⁸，cAMP水平从3±0.8皮摩尔/10⁸升高至31±1.9皮摩尔/10⁸，并抑制胶原诱导的血小板聚集。每单位黄嘌呤氧化酶（一种超氧自由基生成系统）向孵育培养基中添加1微摩尔黄嘌呤可增强两种脂肪酸的作用，而240μM过氧化氢（H₂O₂）则抑制这些作用。这些结果表明：（1）DHLA在抑制血小板聚集方面可能比EPA更有效，据报道EPA可降低某些人群中冠心病的发病率；（2）超氧自由基可能激活血小板环氧化酶系统，增加这些PUFA前列腺素前体的脂质过氧化作用，并可能导致血小板聚集的抑制，而H₂O₂可能具有相反的作用。
