Chisaki Keigo, Okuda Yukichi, Suzuki Seiji, Miyauchi Takashi, Soma Masaaki, Ohkoshi Norio, Sone Hirohito, Yamada Nobuhiro, Nakajima Toshiaki
Department of Internal Medicine, Institute of Clinical Medicine, University of Tsukuba, Tsukuba, Japan.
Hypertens Res. 2003 Aug;26(8):655-61. doi: 10.1291/hypres.26.655.
cis-Polyunsaturated fatty acids such as eicosapentaenoic acid (EPA) are the major fatty acids contained in fish oil, and are known to affect the various physiological properties of cell membranes in humans. The present study investigated the effects of polyunsaturated fatty acids on endothelin-1 (ET-1) production in human umbilical vein endothelial cells (HUVECs) and on insulin activity. After addition of various concentrations of EPA, docosahexaenoic acid, arachidonic acid, or linoleic acid to a culture medium, the concentration of ET-1 was measured using ELISA, and that of ET-1 mRNA was determined by RT-PCR. The results showed that EPA had the strongest inhibitory effect (p<0.05) on both basal ET-1 production and ET-1 mRNA levels. In addition, insulin (1 micromol/l) markedly increased ET-1 production, and EPA also significantly decreased the effect induced by insulin. Pretreatment with Ca2+ chelator EGTA (1 mmol/l), NOS inhibitor L-NAME (300 micromol/l), or calmodulin antagonist W-7 (300 micromol/l) inhibited NO production by EPA (100 micromol/l), but these pretreatments had no effect on ET-1 production by EPA. These findings suggest that EPA reduces basal and insulin-enhanced ET-1 production by inhibiting ET-1 mRNA production. These effects of EPA may contribute to its vasorelaxant and anti-atherosclerotic effects.
顺式多不饱和脂肪酸，如二十碳五烯酸（EPA），是鱼油中的主要脂肪酸，已知其会影响人体细胞膜的各种生理特性。本研究调查了多不饱和脂肪酸对人脐静脉内皮细胞（HUVECs）中内皮素-1（ET-1）产生以及胰岛素活性的影响。在向培养基中添加不同浓度的EPA、二十二碳六烯酸、花生四烯酸或亚油酸后，使用酶联免疫吸附测定法（ELISA）测量ET-1的浓度，并通过逆转录聚合酶链反应（RT-PCR）测定ET-1 mRNA的水平。结果表明，EPA对基础ET-1产生和ET-1 mRNA水平均具有最强的抑制作用（p<0.05）。此外，胰岛素（1微摩尔/升）显著增加ET-1的产生，而EPA也显著降低胰岛素诱导的这种效应。用钙离子螯合剂乙二醇双四乙酸（EGTA，1毫摩尔/升）、一氧化氮合酶抑制剂L-硝基精氨酸甲酯（L-NAME，300微摩尔/升）或钙调蛋白拮抗剂W-7（300微摩尔/升）预处理可抑制EPA（100微摩尔/升）诱导的一氧化氮产生，但这些预处理对EPA诱导的ET-1产生没有影响。这些发现表明，EPA通过抑制ET-1 mRNA的产生来降低基础和胰岛素增强的ET-1产生。EPA的这些作用可能有助于其血管舒张和抗动脉粥样硬化作用。
