赛格列酮能抑制血管紧张素Ⅱ诱导的人内皮细胞表面粘附分子上调  

Ciglitazone Inhibits AngiotensinⅡ-induced Expressions of Adhesion Molecules in Human Endothelial Cells

作　　者：丁月霞[1] 钟赟[1] 孙吉力 刘启才[2] 刘世明[1] 

机构地区：[1]广州医学院附属第二医院心内科,广东省广州市510260 [2]广州医学院分子生物学中心

出　　处：《中国动脉硬化杂志》2006年第11期945-948,共4页Chinese Journal of Arteriosclerosis

基　　金：广东省自然科学基金(04009589)

摘　　要：目的研究赛格列酮对血管紧张素Ⅱ诱导人脐静脉内皮细胞表达细胞间粘附分子1和血管细胞粘附分子1上调的影响。方法以不同浓度的赛格列酮(0.1μmol/L、1μmol/L1、0μmol/L和100μmol/L)预处理人脐静脉内皮细胞24 h,再与10-7mmol/L血管紧张素Ⅱ共孵育12 h。通过半定量逆转录聚合酶链反应和Western Blot分别检测细胞间粘附分子1和血管细胞粘附分子1 mRNA和蛋白表达的情况。结果与血管紧张素Ⅱ组相比,0.1μmol/L和1μmol/L赛格列酮预处理24 h组对血管紧张素Ⅱ诱导人脐静脉内皮细胞表达细胞间粘附分子1 mRNA上调无抑制作用(1.107±0.091比1.104±0.081和1.062±0.051,P>0.05),而10μmol/L和100μmol/L组则有明显的抑制作用(0.814±0.016和0.766±0.026,P<0.01和P<0.001);细胞间粘附分子1蛋白表达分别下调52.9%和55.5%(P<0.01和P<0.001)。而不同浓度的赛格列酮(0.1μmol/L、1μmol/L、10μmol/L和100μmol/L)使血管细胞粘附分子mRNA表达分别下调14.2%、19.5%、45.1%和60.7%(0.1μmol/L时P<0.01,余P<0.001);蛋白表达分别下调17.8%、33.8%、54.5%和58.9%(0.1μmol/L时P<0.01,余P<0.001)。结论赛格列酮抑制血管紧张素Ⅱ上调人脐静脉内皮细胞表达血管细胞粘附分子1,并呈浓度依赖效应;但对细胞间粘附分子1无论是mRNA还是蛋白水平,在低浓度(0.1μmol/L和1μmol/L)时无抑制作用,在较高浓度(10μmol/L和100μmol/L)可有较明显的抑制作用。Aim To exarmine the effects of Ciglitazone on the expressions of intercellular adhesion mollie （ ICAM）-1 and vascular cell adhesion molecule （VCAM）-1 which were upregulated by AngⅡ . Methods Human umbilical vein endotidal cells （hUVEC） at passage 3-5 were pro-incubated for 24 h with Ciglitazone {0.1μmol/L, 1μmol/L, 10 μmol/L, and 100 μmol/L） before stimulated by 10-7mmol/LAngⅡ for 12h. Total RNAw was extracted, and the expression of mRNA and protein of ICAM-1 and VCAM-1 was assessed by RT-PCR and Western Blot respectively. Results Ciglitazone at 0.1 μmol/L- 100 μmol/L significantly attenuated the Ang Ⅱ -induced expression of VCAM-1 （0.1 μmol/L P 〈 0.01, the others P 〈 0.001 ） both in mRNA and protein level. Ciglltazone {0.1 μmol/L,1μpmol/L） have no effects on the expression of ICAM-I{P〉0.05）, but inhibited the Ang Ⅱ-induced expression MICAM-1 at 10 μmol/L or 100 μmol/L{P〈0.01, P〈0.001）. Conclusions Pretreatment of Ciglitazone could inhibit Ang Ⅱ -induced the expression of VCAM-1 and ICAM-1. These findings suggest that PPARTγ agonist,currently used in treatment of type Ⅱ diabetes, may have beneficial effects in modulating inflammatory response in atherosclerosis.

关 键 词：病理学与病理生理学 过氧化体增殖物激活型受体Γ 细胞间粘附分子1 血管细胞粘附分子1 

分 类 号：R363[医药卫生—病理学]