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乔松灵因在短暂性全脑缺血/再灌注大鼠治疗效果方面的特征。

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

机构信息

National Center for Pharmaceutical Screening, Institute of Materia Medica, Chinese Academy of Medical Sciences & Peking Union Medical College, Beijing 100050, PR China.

出版信息

Life Sci. 2011 Mar 14;88(11-12):521-8. doi: 10.1016/j.lfs.2011.01.011. Epub 2011 Jan 22.

DOI:10.1016/j.lfs.2011.01.011
PMID:21262238
Abstract

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 5mg/kg) was administrated intravenously 30 min before ischemia and 30 min, 2h, 6h 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 colorimetric 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 24h 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.

摘要

目的

研究乔松素(pinocembrin)的治疗效果及其在短暂性全脑缺血再灌注(I/R)大鼠中的治疗时间窗。

主要方法

成年雄性 Sprague-Dawley 大鼠通过四血管闭塞法进行 20 分钟的全脑缺血。乔松素(1 和 5mg/kg)分别在缺血前 30 分钟和再灌注后 30 分钟、2 小时、6 小时静脉注射。神经功能评分、脑水含量和尼氏染色的组织学检查用于评估缺血后神经元损伤和乔松素的神经保护作用。通过比色法测定脑组织中超氧化物歧化酶(SOD)、髓过氧化物酶(MPO)的活性和丙二醛(MDA)的含量。采用高效液相色谱-电化学法测定神经递质的变化。

主要发现

乔松素能显著改善全脑 I/R 后 24 小时的神经功能缺损和脑水肿,减轻海马神经元丢失的程度,具有广泛的治疗时间窗。结果发现,乔松素治疗可降低 SOD 活性的代偿性增加,并呈剂量依赖性降低 MDA 水平和 MPO 活性。乔松素治疗可调节兴奋性和抑制性氨基酸之间的代谢平衡。

意义

这些发现表明,乔松素对全脑缺血性损伤具有神经保护作用,且治疗时间窗较宽,这可能与其抗氧化、抗炎和抗兴奋毒性作用有关。

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