Marra F, Riccardi D, Melani L, Spadoni S, Galli C, Fabrizio P, Tosti-Guerra C, Carloni V, Gentilini P, Laffi G
Istituto di Medicina Interna, Università di Firenze, Florence, Italy.
J Hepatol. 1998 Apr;28(4):654-61. doi: 10.1016/s0168-8278(98)80290-0.
BACKGROUND/AIMS: Defective platelet aggregation and reduced platelet production of thromboxane A2, a metabolite of arachidonic acid, are common findings in patients with cirrhosis. We evaluated the effects of dietary supplementation with two combinations of unsaturated fatty acids on platelet function and plasma and membrane fatty acids in patients with liver cirrhosis.
In a double-blind study, 15 patients with cirrhosis and defective aggregation were randomized to receive a 6-week supplementation with gamma-linolenic and linoleic acid (1 g/day of each fatty acid) or with oleic acid and linoleic acid (groups GLA and OA, respectively).
Under baseline conditions, patients showed elevated concentrations of monounsaturated fatty acids and a reduction in polyunsaturated fatty acids. The product/precursor ratios for delta6 and delta5 desaturases, two key enzymes in the pathway leading to arachidonic acid, were significantly reduced in the group of patients. In the GLA group, a significant increase in the levels of dihomo-gamma-linolenic acid (20:3omega6) was observed in plasma and membranes, together with a parallel decrease in the 20:4/20:3omega6 ratio after supplementation. No significant changes were observed in the OA group. The levels of arachidonic acid did not change significantly in either group of patients. Platelet aggregation to collagen was unchanged in the GLA group, but significantly improved in the OA group.
These results show that supplementation with precursors of arachidonic acid is ineffective in elevating plasma or membrane arachidonate levels and does not improve platelet aggregation, suggesting that synthesis of arachidonic acid through the delta5 desaturase cannot be correspondingly activated or that incorporation/retention of the produced fatty acid into lipids is impaired. The increased platelet aggregation in the OA group is likely to be explained by the effect of oleic acid contained in the diet, the effects of which may have been counteracted by the elevation in 20:3omega6, a source of anti-aggregatory prostanoids, in the GLA group.
背景/目的：血小板聚集功能缺陷以及作为花生四烯酸代谢产物的血栓素A2生成减少是肝硬化患者的常见表现。我们评估了两种不饱和脂肪酸组合的膳食补充剂对肝硬化患者血小板功能以及血浆和膜脂肪酸的影响。
在一项双盲研究中，15名存在聚集功能缺陷的肝硬化患者被随机分为两组，分别接受为期6周的γ-亚麻酸和亚油酸（每种脂肪酸1克/天）或油酸和亚油酸补充剂（分别为GLA组和OA组）。
在基线条件下，患者的单不饱和脂肪酸浓度升高，多不饱和脂肪酸减少。导致花生四烯酸生成途径中的两个关键酶——δ6和δ5去饱和酶的产物/前体比值在患者组中显著降低。在GLA组中，血浆和膜中二高-γ-亚麻酸（20:3ω6）水平显著升高，同时补充后20:4/20:3ω6比值平行下降。OA组未观察到显著变化。两组患者的花生四烯酸水平均未显著改变。GLA组中血小板对胶原的聚集未改变，但OA组显著改善。
这些结果表明，补充花生四烯酸前体在提高血浆或膜花生四烯酸水平方面无效，且不能改善血小板聚集，这表明通过δ5去饱和酶合成花生四烯酸不能相应被激活，或者所产生的脂肪酸掺入/保留到脂质中的过程受损。OA组血小板聚集增加可能是由于饮食中所含油酸的作用，而GLA组中作为抗聚集前列腺素来源的20:3ω6升高可能抵消了这种作用。
