Abeywardena M Y, Fischer S, Schweer H, Charnock J S
CSIRO, Division of Human Nutrition, Glenthorne Laboratory, O'Halloran Hill, Australia.
Biochim Biophys Acta. 1989 Jun 8;1003(2):161-6. doi: 10.1016/0005-2760(89)90250-6.
Recent studies have shown that ingestion of eicosapentaenoic acid (EPA) in man results in the formation of 'trienoic' prostanoids which amy partly explain the potent antithrombotic/antiatherogenic properties of long-chain polyunsaturated n-3 fatty acids (PUFAs). However, endogenous formation of cyclooxygenase metabolites of EPA has not been demonstrated in an animal model, and in vitro studies indicate a clear species difference in the conversion of EPA to PGI3. Thus, in the present study, the in vivo formation of PGI3 following long-term dietary tuna fish oil supplementation was investigated in a small non-human primate - the marmoset monkey (Callithrix jacchus). The excretion of major urinary metabolites 2,3-dinor-6-keto-PGF1 alpha (PGI2-M) and delta 17-2,3-dinor-6-keto-PGF1 alpha (PGI3-M) was estimated as an index of total body synthesis of PGI2 and PGI3, respectively. Following extraction, dinor prostanoid metabolites were separated by capillary gas chromatography and identified by negative ion chemical ionization mass spectrometry. Supplementation of the standard (reference) diet with either sheep fat or sunflower seed oil did not alter the body production of PGI2-M. However, following the tuna fish oil-enriched diet, there occurred not only an increase in urinary PGI2-M (reference 70.7 +/- 9.0; tuna fish oil 115.5 +/- 12.1 ng/g creatinine, P less than 0.05), but also a considerable formation of PGI3-M (62.9 +/- 5.3 ng/g creatinine), which was not seen in any other dietary group; in addition, the urinary level of immmunoreactive 2,3-dinor-thromboxane B2/3 was reduced after ingestion of tuna fish oil. These urinary changes were accompanied by a rise in plasma phospholipid-bound EPA and docosahexaenoic acid (DHA). In addition, tuna fish oil supplementation resulted in a significant reduction in plasma cholesterol (53%) and triacylglycerols (44%). The present study provides for the first time experimental evidence for the in vivo formation of PGI3 in an animal model and also confirms the earlier observations in man following dietary fish oil supplementation.
最近的研究表明，人类摄入二十碳五烯酸（EPA）会导致“三烯类”前列腺素的形成，这可能部分解释了长链多不饱和n-3脂肪酸（PUFAs）强大的抗血栓/抗动脉粥样硬化特性。然而，在动物模型中尚未证实EPA的环氧化酶代谢产物的内源性形成，并且体外研究表明在EPA转化为前列环素I3（PGI3）方面存在明显的物种差异。因此，在本研究中，在一种小型非人类灵长类动物——狨猴（Callithrix jacchus）中研究了长期膳食补充金枪鱼鱼油后PGI3的体内形成情况。主要尿代谢产物2,3-二去甲-6-酮-前列腺素F1α（PGI2-M）和δ17-2,3-二去甲-6-酮-前列腺素F1α（PGI3-M）的排泄量分别作为PGI2和PGI3全身合成的指标进行估算。提取后，通过毛细管气相色谱法分离二去甲前列腺素代谢产物，并通过负离子化学电离质谱法进行鉴定。用羊脂或葵花籽油补充标准（对照）饮食不会改变PGI2-M的体内生成量。然而，在食用富含金枪鱼鱼油的饮食后，不仅尿中PGI2-M增加（对照70.7±9.0；金枪鱼鱼油115.5±12.1 ng/g肌酐，P＜０.０５），而且还大量形成了PGI3-M（62.9±5.3 ng/g肌酐），这在其他任何饮食组中均未见到；此外，摄入金枪鱼鱼油后，免疫反应性2,3-二去甲血栓素B2/3的尿水平降低。这些尿液变化伴随着血浆磷脂结合的EPA和二十二碳六烯酸（DHA）的增加。此外，补充金枪鱼鱼油导致血浆胆固醇（53%）和三酰甘油（44%）显著降低。本研究首次在动物模型中为PGI3的体内形成提供了实验证据，也证实了早期在人类中关于膳食补充鱼油后的观察结果。
