Rosiglitazone via PPARγ-dependent suppression of oxidative stress attenuates endothelial dysfunction in rats fed homocysteine thiolactone.
Rosiglitazone via PPARγ-dependent suppression of oxidative stress attenuates endothelial dysfunction in rats fed homocysteine thiolactone.
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罗格列酮通过 PPARγ 依赖性氧化应激抑制，减轻喂食同型半胱氨酸硫代内酯的大鼠的内皮功能障碍。
DOI：
10.1111/jcmm.12510
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发表时间：
2015-04
影响因子：
5.3
通讯作者：
Wang SX
中科院分区：
文献类型：
--
作者：
Yang XH;Li P;Yin YL;Tu JH;Dai W;Liu LY;Wang SX
目的探讨选择性过氧化物酶体增殖物激活受体γ（PPARγ）激动剂罗格列酮（RSG）对同型半胱氨酸硫代内酯（HTL）诱导的内皮功能障碍的保护作用及其可能机制。培养的人脐静脉内皮细胞与HTL（1 mM）孵育24小时，显著降低细胞活力测定3-（4，5-二甲基-2-噻唑基）-2，5-二苯基-2-H-四唑溴，以及增强生产的活性氧，核因子κ B的活化，并增加细胞间粘附分子-1分泌。用RSG（0.001-0.1 mM）、吡咯烷二硫代氨基甲酸酯（PDTC，0.1 mM）或夹竹桃苷（0.1 mM）预处理细胞1小时逆转HTL诱导的这些作用。此外，与GW 9662（0.01 mM）共孵育取消了RSG对HTL处理的细胞的保护作用。在离体实验中，暴露于离体主动脉环。大鼠HTL（1 mM）1小时显着损害乙酰胆碱诱导的内皮依赖性舒张，减少释放一氧化氮和超氧化物歧化酶的活性，并增加丙二醛含量在主动脉组织。用RSG（0.1、0.3、1 mM）、PDTC或夹竹桃苷预孵育主动脉环使HTL诱导的疾病正常化。在体内分析表明，RSG（20 mg/kg/d）给药显着抑制氧化应激和预防内皮功能障碍的大鼠喂HTL（50 mg/kg/d）8周。RSG改善喂食HTL的大鼠的内皮功能，这与氧化应激的PPARγ依赖性抑制有关。
To explore whether rosiglitazone (RSG), a selective peroxisome proliferator-activated receptor γ (PPARγ) agonist, exerts beneficial effects on endothelial dysfunction induced by homocysteine thiolactone (HTL) and to investigate the potential mechanisms. Incubation of cultured human umbilical vein endothelial cells with HTL (1 mM) for 24 hrs significantly reduced cell viabilities assayed by 3-(4,5-dimethyl-2-thiazolyl)-2,5-diphenyl-2-H-tetrazolium bromide, as well as enhanced productions of reactive oxygen species, activation of nuclear factor kappa B, and increased intercellular cell adhesion molecule-1 secretion. Pre-treatment of cells with RSG (0.001–0.1 mM), pyrollidine dithiocarbamate (PDTC, 0.1 mM) or apocynin (0.1 mM) for 1 hr reversed these effects induced by HTL. Furthermore, co-incubation with GW9662 (0.01 mM) abolished the protective effects of RSG on HTL-treated cells. In ex vivo experiments, exposure of isolated aortic rings from. rats to HTL (1 mM) for 1 hr dramatically impaired acetylcholine-induced endothelium-dependent relaxation, reduced release of nitric oxide and activity of superoxide dismutase, and increased malondialdehyde content in aortic tissues. Preincubation of aortic rings with RSG (0.1, 0.3, 1 mM), PDTC or apocynin normalized the disorders induced by HTL. In vivo analysis indicated that administration of RSG (20 mg/kg/d) remarkably suppressed oxidative stress and prevented endothelial dysfunction in rats fed HTL (50 mg/kg/d) for 8 weeks. RSG improves endothelial functions in rats fed HTL, which is related to PPARγ-dependent suppression of oxidative stress.
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影响因子：
5.3
作者：
Toaldo C;Pizzimenti S;Cerbone A;Pettazzoni P;Menegatti E;Daniela B;Minelli R;Giglioni B;Dianzani MU;Ferretti C;Barrera G
通讯作者：
Barrera G
影响因子：
20.1
作者：
Wang S;Zhang M;Liang B;Xu J;Xie Z;Liu C;Viollet B;Yan D;Zou MH
通讯作者：
Zou MH
影响因子：
7.7
作者：
Wang S;Xu J;Song P;Viollet B;Zou MH
通讯作者：
Zou MH
影响因子：
2.9
作者：
Jakubowski, H
通讯作者：
Jakubowski, H
影响因子：
64.8
作者：
Kersten, S;Desvergne, B;Wahli, W
通讯作者：
Wahli, W