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黄酮类化合物木犀草素A对小鼠短暂性脑灌注不足所致记忆损伤的影响。

Effect of the flavonoid, oroxylin A, on transient cerebral hypoperfusion-induced memory impairment in mice.

作者信息

Kim Dong Hyun, Jeon Su Jin, Son Kun Ho, Jung Ji Wook, Lee Seungjoo, Yoon Byung Hoon, Choi Ji Woong, Cheong Jae Hoon, Ko Kwang Ho, Ryu Jong Hoon

机构信息

Department of Oriental Pharmaceutical Science and Kyung Hee East-West Pharmaceutical Research Institute, College of Pharmacy, Kyung Hee University, #1 Hoeki-dong, Dongdeamoon-ku, Seoul 130-701, Republic of Korea.

出版信息

Pharmacol Biochem Behav. 2006 Nov;85(3):658-68. doi: 10.1016/j.pbb.2006.10.025. Epub 2006 Dec 14.

DOI:10.1016/j.pbb.2006.10.025
PMID:17174385
Abstract

Oroxylin A is a flavonoid compound that is found in the root of Scutellaria baicalensis Georgi. The aim of this study was to determine the effects of oroxylin A on memory impairment induced by transient bilateral common carotid artery occlusion (2VO) in mice. The ameliorating effect of oroxylin A on memory impairment was investigated using a passive avoidance task, the Y-maze task, and the Morris water maze task in mice. Oroxylin A was found to significantly reverse 2VO-induced cognitive impairments in the passive avoidance and Y-maze tasks in a dose dependant manner (P<0.05). Moreover, oroxylin A (5 mg/kg, p.o.) shortened the escape-latency and prolonged swimming times in the target quadrant during the probe trial in the Morris water maze task (P<0.05). Histochemical and immunohistochemical studies showed that the number of Nissl bodies and OX-42 positive cells in the hippocampal CA1 and dentate gyrus regions were attenuated by oroxylin A. Moreover, phosphorylated cAMP response element-binding protein (CREB) and brain derived neurotrophic factor (BDNF) positive cell numbers were markedly increased in animals treated with oroxylin A than in untreated 2VO controls. These results suggest that oroxylin A dramatically attenuates the memory impairment induced by 2VO, and that this effect may be mediated by the neuroprotective effects of oroxylin A as supported oroxylin A induced reductions in activated microglia and increases in BDNF expression and CREB phosphorylation.

摘要

木犀草素A是一种黄酮类化合物,存在于黄芩的根部。本研究的目的是确定木犀草素A对小鼠双侧颈总动脉短暂闭塞(2VO)诱导的记忆损伤的影响。使用被动回避任务、Y迷宫任务和小鼠莫里斯水迷宫任务研究了木犀草素A对记忆损伤的改善作用。发现木犀草素A以剂量依赖性方式显著逆转2VO诱导的被动回避和Y迷宫任务中的认知损伤(P<0.05)。此外,在莫里斯水迷宫任务的探索试验中,木犀草素A(5mg/kg,口服)缩短了逃避潜伏期并延长了在目标象限的游泳时间(P<0.05)。组织化学和免疫组织化学研究表明,木犀草素A使海马CA1和齿状回区域的尼氏体数量和OX-42阳性细胞数量减少。此外,与未处理的2VO对照相比,用木犀草素A处理的动物中磷酸化的环磷酸腺苷反应元件结合蛋白(CREB)和脑源性神经营养因子(BDNF)阳性细胞数量明显增加。这些结果表明,木犀草素A显著减轻2VO诱导的记忆损伤,并且这种作用可能由木犀草素A的神经保护作用介导,这得到了木犀草素A诱导的活化小胶质细胞减少以及BDNF表达和CREB磷酸化增加的支持。

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