The characteristics of therapeutic effect of pinocembrin in transient global brain ischemia/reperfusion rats

The characteristics of therapeutic effect of pinocembrin in transient global brain ischemia/reperfusion rats
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DOI:
10.1016/j.lfs.2011.01.011
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发表时间:
2011-03-14
期刊:
影响因子:
6.1
通讯作者:
Du, Guan-hua
Du, Guan-hua
中科院分区:
医学2区
文献类型:
--
作者:
Shi, Li-li;Chen, Bai-nian;Du, Guan-hua

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目的:本实验研究了松属素对短暂性全脑缺血/再灌注(I/R)大鼠的治疗作用及其治疗时间窗。于缺血前30 min及再灌注后30 min、2 h、6 h分别静脉注射松素1和5 mg/kg。采用神经功能评分、脑水肿和尼氏染色观察脑缺血后神经元损伤及松属素的神经保护作用。比色法测定脑组织超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)活性及丙二醛(MDA)含量。通过高效液相色谱-电化学方法测定神经递质的改变。主要发现:Pinocembrin显着改善神经功能缺损和脑水肿,并减轻海马神经元丢失的程度在24小时后,全球脑I/R具有广泛的治疗时间窗。结果表明,松属素处理可抑制SOD活性的代偿性升高,并呈剂量依赖性地降低MDA水平和MPO活性。兴奋性和抑制性氨基酸之间的代谢平衡被调制pinocembrin treatment.Significance:这些研究结果表明,pinocembrin提供了一个广泛的治疗时间窗,这可能是由于其抗氧化,抗兴奋性和抗兴奋性毒性作用对全球脑缺血损伤的神经保护。(C)2011爱思唯尔有限公司版权所有。
Aims: The therapeutic effect of pinocembrin, together with the therapeutic time window, in the transient global cerebral ischemia/reperfusion (I/R) rats was investigated.Main methods: Adult male Sprague-Dawley rats were subjected to global cerebral ischemia for 20 min by four-vessel occlusion. Pinocembrin (1 and 5 mg/kg) was administrated intravenously 30 min before ischemia and 30 min, 2 h, 6 h after reperfusion, respectively. Neurological scores, brain edema and histological examination by Nissl staining were employed to assess the neuronal injury after ischemia and the neuroprotection by pinocembrin. The activities of superoxide dismutase (SOD), myeloperoxidase (MPO) and the content of malondialdehyde (MDA) in brain tissue were tested by calorimetric assays. Alterations of neurotransmitters were determined by a high performance liquid chromatography-electrochemical method.Key findings: Pinocembrin significantly ameliorated neurological deficits and brain edema, and alleviated the degree of hippocampal neuronal loss at 24 h after global cerebral I/R with a broad therapeutic time window. It was found that treatment with pinocembrin reduced the compensatory increase of SOD activity and decreased the MDA level and MPO activity in a dose-dependent manner. The metabolic balance between excitatory and inhibitory amino acids was modulated by pinocembrin treatment.Significance: These findings suggest that pinocembrin provides neuroprotection against global cerebral ischemic injury with a wide therapeutic time window, which may be attributed to its antioxidative, antiinflammatory and antiexcitotoxic effects. (C) 2011 Elsevier B.V. All rights reserved.