Scutellarin protects against Aβ-induced learning and memory deficits in rats: involvement of nicotinic acetylcholine receptors and cholinesterase
Scutellarin protects against Aβ-induced learning and memory deficits in rats: involvement of nicotinic acetylcholine receptors and cholinesterase
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DOI：
10.1038/aps.2011.115
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发表时间：
2011-12-01
影响因子：
8.2
通讯作者：
Wang, Yong-lin
中科院分区：
文献类型：
--
作者：
Guo, Li-li;Guan, Zhi-zhong;Wang, Yong-lin
目的：目的：探讨灯盏乙素（Scu）对β-淀粉样肽（A β）所致大鼠学习记忆障碍的保护作用。方法：雄性Wistar大鼠50只，随机分为5组：对照组、假手术组、A β组、A β +Scu组、A β +吡拉西坦组。将β（25-35）注射到侧脑室（每侧10 μ g）。A β治疗后，每天灌胃Scu（10 mg/2 mL）或吡拉西坦（10 mg/2 mL），连续20天。采用Morris水迷宫实验评价大鼠的学习记忆能力。采用Western blotting和real-time PCR分别检测了脑中烟碱乙酰胆碱受体（nAChR）α 4、α 7和β 2亚基的蛋白和mRNA水平。结果：与对照组和假手术组相比，A β组大鼠逃避潜伏期和首次穿越平台时间明显延长，穿越平台总次数明显减少; Scu和吡拉西坦治疗均显著缩短逃避潜伏期和穿越平台时间，增加穿越平台次数，但A β +Scu组和A β +吡拉西坦组之间无显著差异。A β组大鼠大脑皮层nAChR α 4和α 7亚单位蛋白水平较对照组和假手术组分别降低42%~ 47%和58%~ 61%。与A β组相比，Scu处理导致α 4和α 7亚基蛋白分别上调约24%和30%，但A β +Scu和A β +吡拉西坦组之间无显著差异。各组nAChR β 2亚单位蛋白水平无显著性差异。nAChR α 4、α 7和β 2亚基的mRNA水平没有显著变化。与对照组和假手术组相比，A β组脑内AChE和BuChE活性显著升高，血浆中AChE和BuChE活性显著降低。Scu或吡拉西坦治疗恢复的活动，在脑和血浆中接近的水平，在control group.Conclusion：结果表明，Scu可能会拯救一些有害的影响，A β，可能通过刺激nAChR蛋白翻译和调节胆碱酯酶活性。
Aim: To examine the protective effects of scutellarin (Scu) on rats with learning and memory deficit induced by beta-amyloid peptide (A beta).Methods: Fifty male Wistar rats were randomly divided into 5 groups: control, sham operation, A beta, A beta+Scu, and A beta+piracetam groups. A beta(25-35) was injected into the lateral ventricle (10 mu g each side). Scu (10 mg/2 mL) or piracetam (10 mg/2 mL was intragastrically administered per day for 20 consecutive days following A beta treatment. Learning and memory was assessed with Morris water maze test. The protein and mRNA levels of nicotinic acetylcholine receptor (nAChR) alpha 4, alpha 7, and beta 2 subunits in the brain were examined using Western blotting and real-time PCR, respectively. The activities of acetylcholinesterase (AChE) and butyrylcholinesterase (BuChE) in the brain and plasma were measured using Ellman's colorimetric method.Results: In A beta group, the escape latency period and first platform cross was significantly increased, and the total number of platform crossings was significantly decreased, as compared with the control and the sham operation groups. Both Scu and piracetam treatment significantly reduced the escape latency period and time to cross platform, and increased the number of platform crosses, but there were no significant differences between A beta+Scu and A beta+piracetam groups. In A beta group, the protein levels of nAChR alpha 4 and alpha 7 subunits in the cerebral cortex were significantly decreased by 42%-47% and 58%-61%, respectively, as compared to the control and the sham operation groups. Scu treatment caused upregulation of alpha 4 and alpha 7 subunit proteins by around 24% and 30%, respectively, as compared to A beta group, but there were no significant differences between A beta+Scu and A beta+piracetam groups. The protein level of nAChR beta 2 subunit had no significant difference among different groups. The mRNA levels of nAChR alpha 4, alpha 7, and beta 2 subunits were not significantly changed. In A beta group, the activities of AChE and BuChE in the brain were significantly increased, but were significantly decreased in the plasma, as compared to the control and the sham operation groups. Scu or piracetam treatment restored the activities in brain and plasma nearly to the levels in the control group.Conclusion: The results suggest that Scu may rescue some of the deleterious effects of A beta, possibly by stimulating nAChR protein translation and regulating cholinesterase activity.