Synergistic benefit of combined amlodipine plus atorvastatin on neuronal damage after stroke in Zucker metabolic rat
Synergistic benefit of combined amlodipine plus atorvastatin on neuronal damage after stroke in Zucker metabolic rat
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DOI：
10.1016/j.brainres.2010.10.046
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发表时间：
2011-01-12
期刊：
影响因子：
2.9
通讯作者：
Abe, Koji
中科院分区：
文献类型：
--
作者：
Kawai, Hiromi;Deguchi, Shoko;Abe, Koji
中风是一种主要的神经系统疾病，也是世界上死亡的主要原因。我们比较了氨氯地平 (AM) 和阿托伐他汀 (AT) 单一或联合治疗在这种代谢综合征模型 Zucker 大鼠中短暂大脑中动脉闭塞 (tMCAO) 90 分钟后的神经保护作用。动物用载体、AM、AT或AM加AT的组合预处理28天，并在tMCAO 24小时时进行梗塞体积和免疫组织化学分析。 AM 加 AT 治疗的组合比 AM 或 AT 的单独治疗更能减少梗塞体积。与单一AM或AT治疗组相比，联合治疗组中氧化应激标志物如8-羟基-2'-脱氧鸟苷（8-OHdG）、4-羟基-2-壬烯醛（4-HNE）和晚期糖基化产物（AGE）和炎症标志物如肿瘤坏死因子α（TNF-α）和单核细胞趋化蛋白-1（MCP-1）的阳性细胞数量显着减少。本研究表明，单一AM或AT治疗显示出具有抗氧化和抗炎机制的神经保护作用，但AM加AT联合治疗在急性缺血性神经损伤中表现出进一步的协同效益。 (C) 2010 爱思唯尔 BM。版权所有。
Stroke is a major neurologic disorder and a leading cause of death in the world. We compared neuroprotective effects of single or combination therapy of amlodipine (AM) and atorvastatin (AT) in such a metabolic syndrome model Zucker rat after 90 min of transient middle cerebral artery occlusion (tMCAO). The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28 days, and at 24 h of tMCAO, infarct volume and immunohistochemical analyses were performed. The combination of AM plus AT treatment decreased the infarct volume stronger than each single treatment with AM or AT. The numbers of positive cells of oxidative stress markers such as 8-hydroxy-2'-deoxyguanosin (8-OHdG), 4-hydroxy-2-nonenal (4-HNE), and advanced end glycation products (AGE) and inflammation markers such as tumor necrosis factor alpha (TNF-alpha) and monocyte chemoattractant protein-1 (MCP-1) decreased dramatically in the combination-treated group compared with single AM or AT-treated group. The present study showed that single AM or AT treatment showed neuroprotective effects both with antioxidative and anti-inflammatory mechanisms, but combination therapy of AM plus AT presented a further synergistic benefit in acute ischemic neural damages. (C) 2010 Elsevier BM. All rights reserved.