赛格列酮对HUVECs表达eNOS和NO生成的作用  

Ciglitazone enhances endothelial nitric oxide synthase expression and increases NO realse in HUVECs

作　　者：丁月霞[1] 刘世明 钟赟 

机构地区：[1]广州医学院附属第二医院心内科 [2]广东省荣军医院急诊科

出　　处：《中国心血管病研究》2006年第9期697-700,共4页Chinese Journal of Cardiovascular Research

基　　金：广东省自然科学基金课题(04009589)

摘　　要：目的探讨过氧化物酶体增殖因子活化受体γ(PPARγ)激动剂赛格列酮,对血管紧张素Ⅱ(AngⅡ)诱导的人脐静脉内皮细胞(HUVECs)表达一氧化氮合酶(eNOS)及其一氧化氮(NO)生成的影响。方法体外培养HUVECs,用1×10-6～10-4mol/L赛格列酮预处理HUVECs24h,再与10-7mol/LAngⅡ共同孵育12h;通过RT-PCR和WesternBlot分别检测eNOSmRNA和蛋白表达水平;通过Griees反应测定上清NO释放量。结果与无刺激组比较,10-7mol/LAngⅡ刺激HUVECs12h后明显抑制eNOSmRNA及蛋白表达,P<0.001;基础状态下,HUVECseNOSmRNA及其蛋白表达较强,10-7mol/LAngⅡ刺激12h后明显下调eNOSmRNA和蛋白表达(与对照组相比,P<0.001)。各浓度赛格列酮预处理24h明显减弱AngⅡ对HUVECseNOSmRNA的下调作用(与AngⅡ组相比,P<0.001)。同样赛格列酮也明显减弱AngⅡ对HUVECseNOS蛋白表达的下调作用(与AngⅡ组相比,0.1、1μmol/L时P<0.01,10、100μmol/L时P<0.001,但0.1、1、10μmol/L赛格列酮组间比较P>0.05)。与无刺激组比较10-7mol/LAngⅡ明显减少NO的释放,P<0.05;与AngⅡ组比较,赛格列酮干预24h后呈浓度趋势增加NO的释放,P<0.001。结论赛格列酮呈浓度效应上调HUVECs表达eNOS,并呈浓度趋势增加内皮NO的释放。Objective Peroxisome proliferator-activated receptor gamma（PPARγ） ligands reduce lesion formation in animal models of atherosclerosis by mechanisms that have not been defined completely. We hypothesized that PPARγ ligands stimulate endothelial-derived nitric oxide release （eNO） to protect the vascular wall which may be related to the enhancement on expression of endothelial nitric oxide synthase （eNOS）. Methods Human umbilical vein was isolated and culcured.Passage 3- 5 of cultured HUVECs were preincubated for 24 h with Cig （0.1 mol/L, 1 mol/L, 10 mol/L, 100 mol/L）,then incubated with 10-7 mol/L AngⅡ for 12 h. Total RNA was extracted, and eNOS expression both mRNA and protein was assessed by RT-PCR and Western Blot. NO production was measured via griess reaction. Results Ciglitazone markedly enhanced the expression of Ang Ⅱ-reduced eNOS （P〈0.01, P〈0.001 ） ,both mRNA and protein level, and stimulated NO release from human umbilical vein endothelial cells activated by Angiotensin Ⅱ （0.1 mol/L, 1 mol/L ciglitazone P〈0.01, 10 mol/L, 100 mol/L P〈0.001）. Conclusion Taken together, these findings demonstrate that PPARγ ligands ciglitazone could enhance the expression of eNOS inhibited by Ang Ⅱ ,and stimulated NO release from HUVECs,which maybe correlate to a transcriptional mechanism of eNOS expression

关 键 词：过氧化物酶类 过氧化物酶体增剂 一氧化氮合酶 一氧化氮 

分 类 号：R543.5[医药卫生—心血管疾病]