神经生长因子依赖的 TrkA 通路激活：羟乙基芦丁对 D-半乳糖处理小鼠的神经保护作用机制。
NGF-Dependent activation of TrkA pathway: A mechanism for the neuroprotective effect of troxerutin in D-galactose-treated mice.
机构信息
Xuzhou Normal University, Jiangsu Province, China.
出版信息
Brain Pathol. 2010 Sep;20(5):952-65. doi: 10.1111/j.1750-3639.2010.00397.x. Epub 2010 Mar 19.
Abstract
D-galactose-(D-gal)-treated mouse, with cognitive impairment, has been used for neurotoxicity investigation and anti-neurotoxicity pharmacology research. In this study, we investigated the mechanism underlying the neuroprotective effect of troxerutin. The results showed that troxerutin improved behavioral performance in D-gal-treated mice by elevating Cu, Zn-superoxide dismutases (Cu, Zn-SOD) activity and decreasing reactive oxygen species levels. Furthermore, our results showed that troxerutin significantly promoted nerve growth factor (NGF) mRNA expression which resulted in TrkA activation. On one hand, NGF/TrkA induced activation of Akt and ERK1/2, which led to neuronal survival; on the other hand, NGF/TrkA mediated CaMKII and CREB phosphorylation and increased PSD95 expression, which improved cognitive performance. However, the neuroprotective effect of troxerutin was blocked by treatment with K252a, an antagonist for TrkA. No neurotoxicity was observed in mice treated with K252a or troxerutin alone. In conclusion, administration of troxerutin to D-gal-injected mice attenuated cognitive impairment and brain oxidative stress through the activation of NGF/TrkA signaling pathway.
摘要
用 D-半乳糖（D-gal）处理的认知障碍小鼠已被用于神经毒性研究和抗神经毒性药理学研究。在这项研究中，我们研究了曲克芦丁的神经保护作用机制。结果表明，曲克芦丁通过提高 Cu，Zn-超氧化物歧化酶（Cu，Zn-SOD）的活性和降低活性氧水平，改善了 D-gal 处理小鼠的行为表现。此外，我们的结果表明，曲克芦丁显著促进了神经生长因子（NGF）mRNA 的表达，从而激活了 TrkA。一方面，NGF/TrkA 诱导 Akt 和 ERK1/2 的激活，导致神经元存活；另一方面，NGF/TrkA 介导 CaMKII 和 CREB 的磷酸化，并增加 PSD95 的表达，从而改善认知表现。然而，用 K252a（TrkA 的拮抗剂）处理可阻断曲克芦丁的神经保护作用。用 K252a 或曲克芦丁单独处理的小鼠未观察到神经毒性。总之，向 D-gal 注射小鼠给予曲克芦丁可通过激活 NGF/TrkA 信号通路减轻认知障碍和大脑氧化应激。
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