Treatment of Experimental Thrombosis by Intravenous Infusion of Trieicosapentaenoyl Glycerol

从沙丁鱼肌肉中提纯二十碳五烯酸(EPA)，并将其酰化为甘油。将合成的三二十碳五烯酰甘油(EPA-TG)与蛋黄卵磷脂进行乳化。进一步加入甘油(2.5%)以维持乳状液的渗透压。兔(3~3.5 kg)耳缘静脉滴注该乳剂30ml(3g EPA)。分别于用药前、用药后6、24、168h采集耳动脉血标本。制备多形核白细胞，刺激钙离子载体。将上清液提取为白三烯B_4和B_5(LTB4/5)，并用高效液相色谱法进行测定。在对照实验中，用市售大豆油乳剂代替EPA乳剂，EPA输注后6、24和168 h白细胞产生LTB_4的平均水平分别为输注前的60%、72%和86%。LTB_5在输注前低于检测下限，在输注后6h与LTB_4相似，之后下降。在对照试验中，LTB_4的产量没有明显变化。LTB_4(而不是LTB_5)是一种强烈的趋化和聚集白细胞的物质，与急性炎症(包括急性心肌梗死和移植物排斥反应)引起的组织损伤密切相关。输注EPA可迅速抑制LTB_4的产生。因此，EPA乳剂可能对上述临床情况有用。

Eicosapentaenoic acid (EPA) was purified from muscle of sardine and acylated to glycerol. Trieicosapentaenoyl-glycerol (EPA-TG) syntherized this way was emulsified with egg yolk lecithin. Glycerol (2.5%) was further added to maintain osmotic pressure of the emulsion. To rabbits (3-3.5kg) was infused 30ml of the emulsion (3g EPA) through ear veins. Blood samples were obtained from ear arteries before, and 6, 24 and 168 h after the infusion. Polymorphonuclear leukocytes were prepared and stimulated calcium ionophore. The supernatant was extracted for leukotriene B_4 and B_5 (LTB4/5) and measured by high performance liquid chromatography. In the control experiments commercially available soybean oil emulsion was used instead of EPA emulsion.Averaged LTB_4 production by leukocytes 6, 24 and 168 h after EPA infusion was 60 (p<0.05), 72 and 86% of the pre-infusion levels, respectively. LTB_5 production, which was below the detection limits before the infusion, was similar to that of LTB_4 6 h after the infusion, and then decreased afterward. In the control experiments there were no significant changes in LTB_4 production. LTB_5 production was below the detection limits throughout the control experiments.LTB_4 (but not LTB_5) is a potent chemoattractant and aggregant of leukocytes, and intimately related with tissue damage due to acute inflammation (including acute myocardial infarction and graft rejection). Infusion of EPA can depress LTB_4 production very quickly. Consequently, EPA emulsion may be useful for the clinical situations described above.