花生四烯酸表氧化酶代谢产物EETs促内皮细胞的增殖
细胞增殖,,表氧化酶；EETs；内皮细胞；细胞增殖,1材料与方法,2结果,3讨论,参考文献
摘 要 目的 研究花生四烯酸表氧化酶及其代谢产物环氧二十碳烯酸(EETs) 对牛主动脉内皮细胞(BAECs)增殖的影响及机制。方法 BAECs使用腺相关病毒介导的表氧化酶转染或给予EETs，或同时给予信号转导抑制剂，分别行细胞计数、噻唑蓝比色法(MTT)检测、流式细胞仪检测。结果 表氧化酶转染或EETs刺激均显著促进BAECs的增殖并呈剂量依赖效应，而氧化亚氮合酶抑制剂、胞外信号调节蛋白激酸1/2(extracellular siynalregulated kinase,ERK)和磷脂酰肌醇3-激酸(phosphatidylinositol 3kinase,PI3K)均可显著抑制上述效应。结论 EETs可显著促进BAECs增殖，其作用由ERK和PI3K介导，部分由EETs上调的NO介导。关键词 表氧化酶；EETs；内皮细胞；细胞增殖
Arachidonic acid epoxygenase metabolites stimulate endothelial cell growth
WANG Yan, WANG Jianing, WANG Daowen
(Cardiovascular Section, Internal Medicine Department of Tongji Hospital, Tongji Medical College, Huazhong University of Science and Technology, Wuhan 430030,China)
Abstract Objective To study proliferation effects of arachidonic acid epoxygenase metabolites epoxyeicosatrienoic acids (EETs) and relevant signaling pathways. Methods Bovine endothelial cells (BAECs) were incubated with EETs or transfected with recombinant adenoassociated virus vectors containing CYP2J2, CYPF87V, CYP2C11, and GFP (control), respectively, to produce endogenous EETs. The effects of exogenous and endogenous EETs on BAEC capillary formation were investigated. Potential involvement of signaling pathways of the effects was explored by using related inhibitors of the signal molecules. Results EETs markedly promoted BAEC proliferation. Our results also revealed that the effects were significantly attenuated by inhibitors of ERK/MEK or PI3 kinase/Akt, and also partially by endothelial nitric oxide synthase inhibitor, but not by protein kinase C inhibitor. Conclusion AA CYP epoxygenase metabolites EETs, could markedly promote endothelial cell proliferation. The effects are mediated by MAP kinase and PI3 kinase/Akt signaling pathways and partially by regulation of eNOS. ......
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