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亚精胺和精胺通过诱导 SAMP8 小鼠自噬来延缓大脑衰老。

Spermidine and spermine delay brain aging by inducing autophagy in SAMP8 mice.

机构信息

Science and Technology Innovation Center, Guangzhou University of Chinese Medicine, Guangzhou, China.

Institute of Clinical Pharmacology, Guangzhou University of Chinese Medicine, Guangzhou, China.

出版信息

Aging (Albany NY). 2020 Apr 8;12(7):6401-6414. doi: 10.18632/aging.103035.

DOI:10.18632/aging.103035
PMID:32268299
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC7185103/
Abstract

The natural polyamine spermidine and spermine have been reported to ameliorate aging and aging-induced dementia. However, the mechanism is still confused. An aging model, the senescence accelerated mouse-8 (SAMP8), was used in this study. Novel object recognition and the open field test results showed that oral administration of spermidine, spermine and rapamycin increased discrimination index, modified number, inner squares distance and times. Spermidine and spermine increased the activity of SOD, and decreased the level of MDA in the aging brain. Spermidine and spermine phosphorylate AMPK and regulate autophagy proteins (LC3, Beclin 1 and p62). Spermidine and spermine balanced mitochondrial and maintain energy for neuron, with the regulation of MFN1, MFN2, DRP1, COX IV and ATP. In addition, western blot results (Bcl-2, Bax and Caspase-3, NLRP3, IL-18, IL-1β) showed that spermidine and spermine prevented apoptosis and inflammation, and elevate the expression of neurotrophic factors, including NGF, PSD95and PSD93 and BDNF in neurons of SAMP8 mice. These results indicated that the effect of spermidine and spermine on anti-aging is related with improving autophagy and mitochondrial function.

摘要

天然多胺亚精胺和精胺已被报道可改善衰老和衰老引起的痴呆。然而，其机制仍不清楚。本研究使用衰老加速模型小鼠 8（SAMP8）。新颖物体识别和旷场试验结果表明，亚精胺、精胺和雷帕霉素的口服给药增加了辨别指数、修改次数、内平方距离和次数。亚精胺和精胺增加了衰老大脑中的 SOD 活性，并降低了 MDA 的水平。亚精胺和精胺磷酸化 AMPK 并调节自噬蛋白（LC3、Beclin 1 和 p62）。亚精胺和精胺平衡线粒体并为神经元提供能量，调节 MFN1、MFN2、DRP1、COX IV 和 ATP。此外，Western blot 结果（Bcl-2、Bax 和 Caspase-3、NLRP3、IL-18、IL-1β）表明，亚精胺和精胺可预防 SAMP8 小鼠神经元中的细胞凋亡和炎症，并提高神经营养因子的表达，包括 NGF、PSD95 和 PSD93 和 BDNF。这些结果表明，亚精胺和精胺对抗衰老的作用与其改善自噬和线粒体功能有关。

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