花生四烯酸表氧化酶代谢产物促进内皮细胞趋化和迁移

目的研究花生四烯酸表氧化酶代谢产物环氧二十碳四烯酸(epoxyeicosatrlenolc acids，EETs)对牛主动脉内皮细胞(boyine aortic endothelial cells，BAECs)趋化和迁移的影响及机制。方法BAECs给予EETs和(或)信号转导抑制剂，以刮痕修复、Boyrden小室方法检测细胞趋化和迁移的改变。结果EETs均显著促进BAECs的趋化和迁移，并呈剂量依赖效应，而一氧化氮合酶(nitric oxide synthase，NOS)抑制剂、胞外信号调节蛋白激酶1/2(extracellular signal-regulated kinase，ERK)抑制剂和磷脂酰肌醇3-激酶(phosphatidyllnositol 3-kinase，P13K)抑制剂可显著抑制上述效应。结论EETs可显著促进BAECs的趋化和迁移，其作用由MAKP和P13K介导，部分由EETs上调的内皮NOS介导。

EPOXYEICOSATRIENOIC ACIDS PROMOTE CHEMOTAXSIS AND MIGRATION OF ENDOTHELIAL CELLS

ObjectiveTo study the effects of arachidonic acid epoxygenase metabolites epoxyeicosatrienoic acids(EETs) on bovine aortic endothelial cells(BAECs) chemotaxis and migration. MethodsBAECs were incubated with EETs or nitric oxide synthase inhibitor. Effects of EETs on BAEC chemotaxis and migration were investigated. Potential involvment of signaling pathways of those effects were explored by using related inhibitors of the signal molecules. ResultsEETs markedly promoted BAECs chemotaxis and migration in a dose-dependent manner. The results also revealed that those effects were significantly attenuated by inhibitors of extracellular signal-regulated kinase(ERK), phosphatidylinositol 3-kinase(PI3K), and also partially by endothelial nitric oxide synthase inhibitor, but not by protein kinase C inhibitor. ConclusionEETs markedly promote BAECs chemotaxis and migration. These effects are involved in MAKP kinase and PI3 kinase/Akt signaling pathways and partially in regulation of endothelial nitric oxide synthase.