Different effect of acute treatment with rosiglitazone on rat myocardial ischemia/reperfusion injury by administration method
Different effect of acute treatment with rosiglitazone on rat myocardial ischemia/reperfusion injury by administration method
复制标题
DOI：
10.1016/j.ejphar.2008.05.005
复制
发表时间：
2008-07-28
影响因子：
5
通讯作者：
Wada, Koichiro
中科院分区：
文献类型：
--
作者：
Abe, Masahiro;Takiguchi, Yoshiharu;Wada, Koichiro
本研究旨在探讨罗格列酮，过氧化物酶体增殖物激活受体（PPAR）-γ激动剂，使用不同的管理方法，对大鼠心肌缺血30分钟，再灌注4小时诱导的心肌梗死面积的影响。缺血前30 min开始持续静脉滴注罗格列酮（0.5 mg/kg/h）2 h，可明显缩小梗死面积。另一方面，在再灌注前5分钟推注0.75 mg/kg显示出梗死范围的限制，但在闭塞前30分钟推注1 mg则没有。当同时给予抗氧化剂N-乙酰半胱氨酸时，在闭塞前推注罗格列酮可获得保护作用。罗格列酮的心肌保护作用与抑制心肌组织中髓过氧化物酶活性、肿瘤坏死因子-et含量和抑制剂kappa B磷酸化有关。目前的研究表明，罗格列酮对心肌缺血/再灌注损伤的保护作用最可能是通过激活PPAR-gamma抑制核因子-κ B通路。然而，如果在缺血期间罗格列酮的浓度高，则用罗格列酮进行急性治疗是有害的。(c)2008 Elsevier B. V.保留所有权利。
The present study was undertaken to examine the effect of rosiglitazone, a peroxisome proliferator-activated receptor (PPAR)-gamma agonist, using different administration methods, on rat myocardial infarct size induced by 30 min of ischemia followed by 4 h of reperfusion. The infarct size was significantly reduced by the continuous infusion of rosiglitazone (0.5 mg/kg/h) from 30 min before Occlusion for 2 h. On the other hand, limitation of the infarct size was shown by a bolus injection of 0.75 mg/kg at 5 min before reperfusion, but not by a bolus injection of 1 mg at 30 min before occlusion. The protective effect of rosiglitazone by the bolus injection before occlusion was obtained when an antioxidant, N-acetylcysteine, was concomitantly administered. The cardioprotection by rosiglitazone was associated with the inhibition of increased myeloperoxidase activity, tumor necrosis factor-et content and phosphorylation of inhibitor kappa B in the myocardium. The present study demonstrated that the protective effect of rosiglitazone on myocardial ischemia/reperfusion injury occurred most likely by inhibition of the nuclear factor-kappa B pathway through PPAR-gamma activation. However, acute treatment with rosiglitazone is harmful if its concentration is high during ischemia. (c) 2008 Elsevier B.V. All rights reserved.