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丹参素对1-甲基-4-苯基-1,2,3,6-四氢吡啶诱导的帕金森病小鼠模型的神经保护作用

Neuroprotective effects of Danshensu in Parkinson's disease mouse model induced by 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine.

作者信息

Han Bing, Che Xin, Zhao Yue, Li Cuiting, He Jie, Lu Yan, Wang Zhenhua, Wang Tian

机构信息

Center for Mitochondria and Healthy Aging, School of Life Science.

Key Laboratory of Molecular Pharmacology and Drug Evaluation (Yantai University), School of Pharmacy, Ministry of Education, Collaborative Innovation Center of Advanced Drug Delivery System and Biotech Drugs in Universities of Shandong, Yantai University, Yantai, Shandong, People's Republic of China.

出版信息

Behav Pharmacol. 2019 Feb;30(1):36-44. doi: 10.1097/FBP.0000000000000412.

DOI:10.1097/FBP.0000000000000412
PMID:29847337
Abstract

Parkinson's disease (PD) causes major changes in dopaminergic neurons of the brain, resulting in motor symptoms in older adults. A previous study showed that Danshensu alleviates the cognitive decline by attenuating neuroinflammation. In the present study, we investigated the neuroprotective effect of Danshensu in the 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) mouse model of PD. C57BL/6 mice were randomly divided into the following four groups: control, MPTP, Danshensu at 15 mg/kg, and Danshensu at 60 mg/kg. The mice were administered Danshensu intragastrically for 14 days. In the behavioral tests, Danshensu treatment alleviated motor dysfunction induced by MPTP. The number of tyrosine hydroxylase-positive neurons in the substantia nigra was significantly reduced in the MPTP group, relative to the control group; Danshensu partially blocked this reduction in tyrosine hydroxylase-positive neurons. In addition, Danshensu attenuated the reductions in striatal dopamine and 5-HT levels induced by MPTP. Danshensu also diminished the increase in Iba1-positive cells in the substantia nigra and reduced the levels of interleukin-1β and tumor necrosis factor-α in the striatum. These findings suggest that Danshensu exerts neuroprotective effects and improves motor function in PD mice, at least in part, by reducing neuroinflammation.

摘要

帕金森病(PD)会导致大脑中多巴胺能神经元发生重大变化,从而在老年人中引发运动症状。先前的一项研究表明,丹参素可通过减轻神经炎症来缓解认知衰退。在本研究中,我们在1-甲基-4-苯基-1,2,3,6-四氢吡啶(MPTP)诱导的帕金森病小鼠模型中研究了丹参素的神经保护作用。C57BL/6小鼠被随机分为以下四组:对照组、MPTP组、15 mg/kg丹参素组和60 mg/kg丹参素组。小鼠经胃内给予丹参素,持续14天。在行为测试中,丹参素治疗减轻了MPTP诱导的运动功能障碍。与对照组相比,MPTP组黑质中酪氨酸羟化酶阳性神经元的数量显著减少;丹参素部分阻止了酪氨酸羟化酶阳性神经元数量的减少。此外,丹参素减弱了MPTP诱导的纹状体多巴胺和5-羟色胺水平的降低。丹参素还减少了黑质中Iba1阳性细胞的增加,并降低了纹状体中白细胞介素-1β和肿瘤坏死因子-α的水平。这些发现表明,丹参素至少部分地通过减轻神经炎症发挥神经保护作用并改善帕金森病小鼠的运动功能。

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