Department of Neurology, Graduate School of Medicine, Dentistry and pharmaceutical Sciences, Okayama University, 2-5-1 Shikatacho, Okayama 700-8558, Japan.
Brain Res. 2011 Mar 25;1382:308-14. doi: 10.1016/j.brainres.2011.01.062. Epub 2011 Jan 26.
Ischemic stroke is a major neurologic disorder and a leading cause of disability and 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. The animals were pretreated with vehicle, AM, AT, or the combination of AM plus AT for 28days, and physical and serum parameters were analyzed, then 90min of transient middle cerebral artery occlusion (tMCAO), was performed followed by immunohistochemical analyses at 24h. Without affecting serum levels of lipids, adiponectin, and leptin, the combination therapy of AM plus AT ameliorated the post-ischemic brain weight increase. The single treatment with AM or AT itself exerted neuroprotective effects with reducing inductions of MMP-9 and AT2R, as well as with preserving collagen IV, and the combination therapy of AM plus AT showed a further synergistic benefit against acute ischemic neural damages. Single AT was more protective on these 3 molecules than single AM at this time point of 24h after tMCAO. Thus, the combination therapy with AM plus AT extended the neuroprotectives effect of single treatment with AM or AT on a part of neurovascular unit and a hypertension-related receptor.
缺血性脑卒中是一种主要的神经系统疾病，也是世界范围内残疾和死亡的主要原因。我们比较了氨氯地平（AM）和阿托伐他汀（AT）单药或联合治疗在这种代谢综合征模型 Zucker 大鼠中的神经保护作用。动物用载体、AM、AT 或 AM 加 AT 的联合治疗预处理 28 天，分析其生理和血清参数，然后进行 90 分钟短暂性大脑中动脉闭塞（tMCAO），再在 24 小时后进行免疫组织化学分析。联合治疗 AM 加 AT 不影响血清脂质、脂联素和瘦素水平，但可改善缺血后脑重增加。AM 或 AT 单药治疗本身具有神经保护作用，可降低 MMP-9 和 AT2R 的诱导，同时保持胶原 IV，AM 加 AT 的联合治疗对急性缺血性神经损伤显示出进一步的协同作用。在 tMCAO 后 24 小时这个时间点，单 AT 在这 3 个分子上的保护作用强于单 AM。因此，AM 加 AT 的联合治疗扩展了 AM 或 AT 单药治疗对部分神经血管单元和高血压相关受体的神经保护作用。
