花生四烯酸细胞色素P450表氧化酶代谢产物EET抑制脂多糖诱导的内皮细胞凋亡  

Cytochrome P450 Epoxygenase Metabolism of Arachidonic Add Inhibits LPS-Induced Endothelial Cells Apoptosis

作　　者：王勇[1] 陈积雄[1] 杨仕林[1] 汪道文[1] 

机构地区：[1]华中科技大学同济医学院附属同济医院高血压研究所 内科,武汉市430030

出　　处：《中国分子心脏病学杂志》2006年第3期140-144,共5页Molecular Cardiology of China

基　　金：国家自然科学基金项目(No.30430320;30270561);科技部国际合作项目(No.2005DFA30880)资助

摘　　要：目的研究花生四烯酸经细胞色素P450表氧化酶代谢产物一表氧化二十碳三烯酸 (epoxyeicosatrienoic acids,EETs)对脂多糖(lipopolysaccharide,LPS)诱导的牛主动脉内皮细胞(bovine aortic endothelial cells,BAECs)凋亡的影响。方法原代分离培养BAECs。分别在细胞培养基中加入 8,9-,11,12-,和14,15-EET1 h后,用LPS(100 ng／ml)诱导内皮细胞凋亡。用MTT法检测LPS对 BAECs的毒性作用,再通过细胞形态学(吖啶橙／溴化乙锭染色)和流式细胞仪计数检测其凋亡变化。结果LPS对BAECs的毒性作用呈剂量依赖性和时间依赖性。LPS可明显诱导BAECs凋亡,但8, 9-,11,12-,和14,15-EET干预的BAECs凋亡细胞数分别为(37．03±3．014)％、(33．45±7．918)％和 (35．75±7．858)％明显少于溶媒对照组(47．33±3．154)％。结论这些结果证明了花生四烯酸细胞色素P450表氧化酶代谢产物EETs能明显的抑制LPS诱导的BAECs凋亡。这表明细胞色素P450 表氧化酶可能有保护心血管系统,防止其受到炎症损伤和粥样硬化的作用。Objective To observe the effect of arachidonic acid cytochrome P450 expoxygenases （CYP450） metabolite, epoxyeicosatrienoic acids （EETs）, on the apoptosis of primarily cultured bovine aortic endothelial cells （BAECs） induced by lipopolysaccharide （LPS）. Method BAECs were separated from bovine aorta and cultured. 8, 9-, 11,12- and 14,15-EET （100nM） were added into the culture medium of BAECs, respectively, followed by LPS treatments （100 ng/ml）. The toxicity of LPS on BAECs was evaluated using MTF colorimetric assay BAEC apoptosis was detected using morphological observations （Acridine Orange/Ethidium Bromide staining） and flow cytometry assay. Result LPS treatment significantly induced BAEC apoptosis, but incubation with 8,9-, 11,12-, and 14, 15-EET markedly attenuated LPS-induced BAEC apoptosis （ 37.03±3. 014）%, （33.45±7. 918）% and （35.75±7. 858） % , respectively compared with vehicle control （47.33%±3. 154% ）. Conclusion These results indicate that CYP expoxygenases metabolite EETs significantly protect endothelial cells and attenuate LPS-induced BAECs apoptosis, which suggests that CYP epoxygenases may protect cardiovascular system from inflammatory injury and atherosclerosis.

关 键 词：牛主动脉内皮细胞 脂多糖 凋亡 表氧化二十碳三烯酸 

分 类 号：R363[医药卫生—病理学]