Modulation of cardiac and aortic peroxisome proliferator-activated receptor-γ expression by oxidative stress in chronically glucose-fed rats
Modulation of cardiac and aortic peroxisome proliferator-activated receptor-γ expression by oxidative stress in chronically glucose-fed rats
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DOI：
10.1016/j.amjhyper.2005.11.006
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发表时间：
2006-04-01
影响因子：
3.2
通讯作者：
de Champlain, J
中科院分区：
文献类型：
--
作者：
El Midaoui, A;Wu, LY;de Champlain, J
背景资料：本研究的目的是研究α-硫辛酸对慢性高血压胰岛素抵抗大鼠心血管组织中增殖物过氧化物酶体激活受体-γ（PPAR-gamma）和PPAR-alpha表达的慢性影响。我们还评估了高水平的胰岛素、葡萄糖或两者对主动脉平滑肌细胞（SMCs）产生超氧阴离子（O-2（-））的慢性效应，以及是否存在PPAR-gamma激动剂吡格列酮。氧化应激的评价通过测量O-2（-）的生产使用光泽精method.Results：增加血压，在主动脉O-2（-）的生产，在葡萄糖或胰岛素水平，在胰岛素抵抗，以及减少PPAR-gamma蛋白水平在主动脉和心脏组织中被阻止或减弱在葡萄糖处理的大鼠喂食硫辛酸。吡格列酮的慢性治疗可防止培养的SMCs中O-2（-）产生的显著增加，这些SMCs长期接受高胰岛素联合或不联合高糖level.Conclusions：抗氧化剂α-硫辛酸的联合治疗可恢复心血管组织中的PPAR-gamma水平，并减弱或防止长期葡萄糖喂养大鼠中胰岛素抵抗和高血压的发展。此外，吡格列酮还可有效预防高胰岛素联合高葡萄糖浓度处理的SMC中氧化应激增加，这一发现支持了以下假设：PPAR-gamma活性的激活可抵消似乎与高血压和胰岛素抵抗的发生有关的氧化应激。(c)2006年美国高血压杂志有限公司
Background: The aim of the present study was to examine the chronic effects of a-lipoic acid on proliferator peroxisome activated receptors-gamma (PPAR-gamma) and PPAR-alpha expressions in cardiovascular tissues of chronically hypertensive insulinoresistant rats. We have also evaluated the chronic effects of high levels of insulin, glucose, or both on superoxide anion (O-2(-)) production in aortic smooth muscle cells (SMCs) in the presence or in absence of pioglitazone, a PPAR-gamma agonist.Methods: The PPAR-gamma and PPAR-a expressions were measured by Western blot. The oxidative stress was evaluated by measuring the O-2(-) production using the lucigenin method.Results: Increases in blood pressure, in aortic O-2(-) production, in glucose or insulin levels, and in insulin resistance, as well as the decrease in PPAR-gamma protein levels in aorta and heart tissues were prevented or attenuated in glucose-treated rats fed with lipoic acid. Chronic treatment with pioglitazone prevented the marked increase in O-2(-) production in cultured SMCs chronically treated with high insulin combined or not with high glucose levels.Conclusions: The combined therapy with the antioxidant alpha-lipoic acid restored PPAR-gamma levels in cardiovascular tissues and attenuated or prevented the development of insulin resistance and hypertension in chronically glucose-fed rats. Moreover, the finding that pioglitazone was also efficient in preventing the increase in oxidative stress in SMCs treated with high insulin combined with high glucose concentrations supports the hypothesis that the activation of PPAR-gamma activity can counteract the oxidative stress that seems to be implicated in the development of hypertension and insulin resistance. (c) 2006 American Journal of Hypertension, Ltd.