Treatment effects of tanshinone IIA against intracerebroventricular streptozotocin induced memory deficits in mice
Treatment effects of tanshinone IIA against intracerebroventricular streptozotocin induced memory deficits in mice
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丹参酮IIA对脑室内链脲佐菌素所致小鼠记忆缺陷的治疗作用
DOI：
10.1016/j.brainres.2015.11.040
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发表时间：
2016-01-15
期刊：
影响因子：
2.9
通讯作者：
Qian, Yihua
中科院分区：
文献类型：
--
作者：
Liu, Chang;Wu, Youxuan;Qian, Yihua
我们前期的研究表明，丹参酮IIA（tanshinone IIA，tan IIA）对β-淀粉样蛋白（beta-amyloid protein，A β）诱导的培养皮层神经元和PC 12细胞的神经毒性具有明显的保护作用。本研究旨在探讨tan HA对链脲佐菌素（STZ）诱导的散发性阿尔茨海默病（AD）模型记忆障碍的保护作用。隔日（第1天和第3天）向小鼠脑室内注射两次STZ（3 mg/kg ICV）。每日用tan IIA（20、40和80 mg/kg，i. g.）从第一剂STZ开始，持续28天，通过Morris水迷宫（MWM）测试评估，显示STZ诱导的记忆缺陷的剂量依赖性改善。Nissl染色结果证实了tan IIA对STZ诱导的大脑皮层和海马神经元损伤具有保护作用。此外，tan IIA还能显著降低STZ引起的顶叶皮层和海马AChE活性和MDA含量的升高，显著抑制STZ引起的顶叶皮层和海马超氧化物歧化酶（SOD）和谷胱甘肽过氧化物酶（GSH-Px）活性的降低，并减弱顶叶皮层和海马p38丝裂原活化蛋白激酶（MAPK）的磷酸化。这些结果表明，tan IIA预防STZ诱导的记忆缺陷可能归因于改善神经元损伤，恢复胆碱能功能，减轻氧化应激和阻断p38 MAPK信号通路激活。基于我们以前的研究，本研究提供了进一步的支持，在治疗AD的潜在用途tan IIA。(C)2015 Elsevier B. V.版权所有。
Our previous studies demonstrated that tanshinone IIA (tan IIA) has significant protective effects against the neurotoxicity induced by beta-amyloid protein (A beta) in cultured cortical neurons and PC12 cells. This study was designed to investigate the protective effects of tan HA against memory deficits induced by streptozotocin (STZ) in a model of sporadic Alzheimer's disease (AD). STZ was injected twice intracerebroventrically (3 mg/kg ICV) on alternate days (day 1 and day 3) in mice. Daily treatment with tan IIA (20, 40, and 80 mg/kg, i.g.) starting from the first dose of STZ for 28 days showed a dose dependent improvement in STZ induced memory deficits as assessed by Morris water maze (MWM) test. Nissl staining results confirmed the protective effects of tan IIA on cerebral cortical and hippocampal neurons damage induced by STZ. In addition, tan IIA markedly reduced STZ induced elevation in acetylcholinesterase (AChE) activity and malondialdehyde (MDA) level, and significantly inhibited STZ induced reduction in superoxide dismutases (SOD) and glutathione peroxidase (GSH-Px) activities in the parietal cortex and hippocampus.Moreover, tan IIA attenuated p38 mitogen activated protein kinase (MAPK) phosphorylation in the parietal cortex and hippocampus. These findings demonstrate that tan IIA prevents STZ induced memory deficits may be attributed to ameliorating neuronal damage, restoring cholinergic function, attenuating oxidative stress and blocking p38 MAPK signal pathway activation. Based on our previous studies, the present study provides further support for the potential use of tan IIA in the treatment of AD. (C) 2015 Elsevier B.V. All rights reserved.