Prevention of neuronal damage by calcium channel blockers with antioxidative effects after transient focal ischemia in rats
Prevention of neuronal damage by calcium channel blockers with antioxidative effects after transient focal ischemia in rats
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DOI：
10.1016/j.brainres.2007.07.038
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发表时间：
2007-10-24
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：
Lukic-Panin, Violeta;Kamiya, Tatsushi;Abe, Koji
背景：脑缺血是世界范围内导致死亡的主要原因，也是致残的首要原因。有很多治疗中风的药物处于实验阶段。其中包括钙通道阻滞剂(CCB)，在动物模型中，它们在修复脑缺血损伤方面具有不同的效果。CCBS在脑缺血中的作用机制尚不清楚，但其抗氧化作用被认为与此有关。在本研究中，我们研究了两种CCBS，氮卓尼地平和氨氯地平的抗氧化和神经保护作用。方法：采用尼龙线栓法建立大鼠大脑中动脉短暂性闭塞(MCAO)模型。动物分为3组，赋形剂组、阿泽尼地平组和氨氯地平组。阿泽尼地平组和氨氯地平组在MCAO前分别给予氮卓尼平(1 mg/kg)和氨氯地平(1 mg/kg)灌胃2周。赋形剂组用甲基纤维素水溶液处理2周。MCAO后24 h处死大鼠。观察生理指标(平均动脉压、心率、体重)、脑梗塞体积、脑水肿指数、脑血流量(CBF)、氧化应激标志物HEL、4-HNE、AGE和8-OHdG，以及TUNEL法检测细胞凋亡情况。结果：两组患者的平均动脉压、心率和体重差异无统计学意义。阿奇尼地平和氨氯地平治疗可减少脑梗塞体积和脑水肿。阿奇尼地平组较氨氯地平组更能明显缩小脑梗塞体积和脑水肿。CCBS组大鼠脑血流无明显衰减。CCBS组HEL、4-HNE、AGE和8-OHdG阳性细胞数显著减少。与氨氯地平组相比，azelNiclipine组的这些分子再次减少。在TUNEL染色中，CCBS处理组的阳性细胞数较少，尤其是氮卓尼利平组。结论：阿奇尼地平和氨氯地平预处理对脑缺血有保护作用。抗氧化性能是CCBS的重要特性之一，与脑保护有关。(C)2007 Elsevier B.V.保留所有权利。
Background: Cerebral ischemia is a major leading cause of death and at the first place cause of disability all over the world. There are a lot of drugs that are in experimental stage for treatment of stroke. Among them are calcium channel blockers (CCBs) that have, in animal models, different effectiveness in healing of ischemic damage in brain. Mechanism of CCBs' action in cerebral ischemia is still unclear, but antioxidative property is supposed to be implicated. In the present study, we investigated antioxidative and neuroprotective properties of two CCBs, azelnidipine and amlodipine. Methods: Male Wistar Kyoto rats were subjected to 90 min of transient middle cerebral artery occlusion (MCAO) by a nylon thread. Animals were divided into 3 groups, vehicle, azelnidipine and amlodipine group. In the azelnidipine and amlodipine groups, rats were treated with azelniclipine (1 mg/kg) and amlodipine (1 mg/kg) by gastric gavage for 2 weeks before MCAO. Vehicle group was treated by solution of methyl cellulose for 2 weeks. Rats were killed 24 h after MCAO. Physiological parameters (mean arterial pressure, heart rate, body weight), infarct volume, brain edema index, cerebral blood flow (CBF), oxidative stress markers which are HEL, 4-HNE, AGE and 8-OHdG, and evidence of apoptosis by TUNEL, were investigated. Results: There were no significant differences among groups in mean arterial pressure, heart rate and body weight. Treatment with azelnidipine and amlodipine reduced infarct volume and brain edema. Azelnidipine treated group showed more marked reduction of infarct volume and cerebral edema than amlodipine group. There was no attenuation of CBF in CCBs groups. The number of HEL, 4-HNE, AGE and 8-OHdG positive cells were significantly decreased in the CCBs treated groups. These molecules were again fewer in the azelniclipine group than in the amlodipine group. In TUNEL staining, the numbers of positive cells was smaller in the CCBs treated groups, especially in the azelniclipine group. Conclusions: Pretreatment of azelnidipine and amlodipine had a neuroprotective effect in ischemic brain. Antioxidative property is one of the important profiles of CCBs that is implicated in brain protection. (C) 2007 Elsevier B.V. All rights reserved.