Paeoniflorin attenuates chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rats
Paeoniflorin attenuates chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rats
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DOI：
10.1016/j.brainres.2006.02.115
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发表时间：
2006-05-17
期刊：
影响因子：
2.9
通讯作者：
Zhu, Xing-Zu
中科院分区：
文献类型：
--
作者：
Liu, Jing;Jin, Dao-Zhong;Zhu, Xing-Zu
慢性脑灌注不足是一种轻度缺血性疾病，与AD的认知功能障碍有关。芍药苷（PF）是芍药根的主要成分，在大脑中动脉闭塞模型中被证明具有神经保护作用。本研究旨在探讨PF对慢性脑低灌注所致大鼠学习功能障碍和脑损伤的保护作用。在永久性双侧颈总动脉闭塞后7周，在Morris水迷宫中测试大鼠。随后，处死动物，用免疫细胞化学法标记海马神经元、星形胶质细胞和小胶质细胞。PF在2.5mg/kg剂量下可改善脑低灌注相关的学习功能障碍，并防止CA 1神经元损伤。慢性脑低灌注可增加海马星形胶质细胞和小胶质细胞的免疫反应性。PF在2.5 mg/kg剂量下可阻止该增加。脑灌注不足也增加了核因子-κ B（NF-κ B）的表达，主要是在星形胶质细胞中，但不是在神经元中。PF（2.5 mg/kg）处理后，海马NF-κ B免疫染色减弱。结果表明PF对慢性脑低灌注所致的认知功能障碍和脑损伤有明显的改善作用。PF对脑内神经炎性反应的抑制可能与其神经保护作用有关。(c)2006 Elsevier B. V.保留所有权利。
Chronic cerebral hypoperfusion, a mild ischemic condition, is associated with the cognitive deficits of AD. Paeoniflorin (PF), a major constituent of peony root, was proved to be neuroprotective in middle cerebral artery occlusion model. In this study, we investigated whether PF could attenuate chronic cerebral hypoperfusion-induced learning dysfunction and brain damage in rat. Seven weeks after permanent bilateral occlusion of the common carotid arteries, the rats were tested in the Morris water maze. Subsequently, the animals were sacrificed and neurons, astrocytes and microglias were labeled with immunocytochemistry in hippocampus. PF at the dose of 2.5 mg/kg ameliorated cerebral hypoperfusion-related learning dysfunction and prevented CA1 neuron damage. Chronic cerebral hypoperfusion increased the immunoreactivity of astrocytes and microglias in hippocampus. The increase was prevented by PF at the dose of 2.5 mg/kg. Cerebral hypoperfusion also increased expression of nuclear factor-kappa B (NF-kappa B), mostly in astrocytes, but not in neurons. With the treatment of PF (2.5 mg/kg), NF-kappa B immunostaining was diminished in hippocampus. Our results demonstrated that PF could attenuate cognitive deficit and brain damage induced by chronic cerebral hypoperfusion. and that suppression of neuroinflammatory reaction in brain might be involved in PF-induced neuroprotection. (c) 2006 Elsevier B.V. All rights reserved.