尼可地尔对内皮细胞氧化应激损伤的保护作用  

Protective effects of nicorandil on oxidative stress-induced injury in endothelial cells

作　　者：雷斌[1] 邹东华[1] 何世安[1] 黄振坚[1] 严翼飞[1] 卢华文[1] 陈昊[1] 

机构地区：[1]中国人民解放军第三○三医院老年病科,南宁530021

出　　处：《中国临床药理学杂志》2013年第7期527-529,共3页The Chinese Journal of Clinical Pharmacology

摘　　要：目的研究尼可地尔对体外内皮细胞氧化应激引起的损伤的保护作用。方法在体外培养基中,加入终浓度为100μmol.L-1的过氧化氢,给予人脐静脉内皮细胞氧化应激暴露24 h。用MTT法检测细胞增殖,Hoechst33258染色观察细胞核形态学,流式细胞仪检测细胞凋亡率,荧光定量分析一氧化氮生成。结果氧化应激引起内皮细胞增殖抑制及细胞核形态异常,使细胞凋亡率从(11.9±3.4)%上升至(78.6±7.6)%。尼可地尔可明显减轻氧化应激引起的细胞增殖抑制及细胞核形态改变,并使细胞凋亡率降低至(48.8±5.1)%;同时尼可地尔可减轻氧化应激引起的内皮细胞一氧化氮生成障碍。尼可地尔的保护效应可被线粒体ATP敏感性钾通道阻断剂5-hydroxydecanoate部分逆转。结论尼可地尔可减轻氧化应激引起的内皮细胞凋亡及功能损害,该保护作用与开放线粒体ATP敏感性钾通道有关。Objective To investigate the protective effects of nicorandil on oxidative stress-induced injury in endothelial cells in vitro.Methods Human umbilical vein endothelial cells（HUVECs） were exposed to oxidative stress by the administration of hydrogen peroxide into the in vitro cultured medium at final dose of 100 μmol.L-1 for 24 h.MTT assay,Hoechst 33258 staining,flow cytometry and quantitative fluorescence analysis of nitric oxide production were performed to examine the cell proliferation,nucleus morphology,rate of cell apoptosis and NO production in endothelial cells,respectively.Results The oxidative stress induced suppression of cell proliferation and abnormal changes in nucleus morphology,and the rate of apoptosis was raised from（11.9 ± 3.4） % to（78.6 ±7.6） %.Nicorandil relieved the suppression of cell proliferation and abnormal changes of nucleus morphology,and significantly decreased the oxidative stress-induced apoptosis to（48.8 ± 5.1） %.Nicorandil also reduced the oxidative stress-induced inhibition of NO production in endothelial cells.The protective effects of nicorandil were partly reversed by 5-hydroxydecanoate,a mitochondrial ATP-sensitive potassium channel blocker.Conclusion Nicorandil reduced oxidative stress-induced apoptosis and dysfunction in endothelial cells,and these protective effects were confirmed to be related to the opening of mitochondrial ATP-sensitive potassium channel.

关 键 词：尼可地尔 内皮细胞 氧化应激 凋亡 

分 类 号：R972.3[医药卫生—药品] R965.1[医药卫生—药学]