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硫化氢供体 L-Dopa 衍生物 ACS84 对 6-OHDA 诱导的帕金森病大鼠模型的治疗作用。

Therapeutic effect of hydrogen sulfide-releasing L-Dopa derivative ACS84 on 6-OHDA-induced Parkinson's disease rat model.

机构信息

Department of Pharmacology, Yong Loo Lin School of Medicine, National University of Singapore, Singapore, Singapore.

出版信息

PLoS One. 2013;8(4):e60200. doi: 10.1371/journal.pone.0060200. Epub 2013 Apr 3.

DOI:10.1371/journal.pone.0060200
PMID:23573240
原文链接:https://pmc.ncbi.nlm.nih.gov/articles/PMC3616069/
Abstract

Parkinson's disease (PD), characterized by loss of dopaminergic neurons in the substantia nigra, is a neurodegenerative disorder of central nervous system. The present study was designed to investigate the therapeutic effect of ACS84, a hydrogen sulfide-releasing-L-Dopa derivative compound, in a 6-hydroxydopamine (6-OHDA)-induced PD model. ACS84 protected the SH-SY5Y cells against 6-OHDA-induced cell injury and oxidative stress. The protective effect resulted from stimulation of Nrf-2 nuclear translocation and promotion of anti-oxidant enzymes expression. In the 6-OHDA-induced PD rat model, intragastric administration of ACS84 relieved the movement dysfunction of the model animals. Immunofluorescence staining and High-performance liquid chromatography analysis showed that ACS84 alleviated the loss of tyrosine-hydroxylase positive neurons in the substantia nigra and the declined dopamine concentration in the injured striatums of the 6-OHDA-induced PD model. Moreover, ACS84 reversed the elevated malondialdehyde level and the decreased glutathione level in vivo. In conclusion, ACS84 may prevent neurodegeneration via the anti-oxidative mechanism and has potential therapeutic values for Parkinson's disease.

摘要

帕金森病（PD）以黑质多巴胺能神经元丧失为特征，是一种中枢神经系统的神经退行性疾病。本研究旨在探讨硫化氢供体 L-Dopa 衍生物化合物 ACS84 在 6-羟多巴胺（6-OHDA）诱导的 PD 模型中的治疗作用。ACS84 可保护 SH-SY5Y 细胞免受 6-OHDA 诱导的细胞损伤和氧化应激。这种保护作用源于 Nrf-2 核易位的刺激和抗氧化酶表达的促进。在 6-OHDA 诱导的 PD 大鼠模型中，腹腔内给予 ACS84 可缓解模型动物的运动功能障碍。免疫荧光染色和高效液相色谱分析显示，ACS84 可减轻 6-OHDA 诱导的 PD 模型中酪氨酸羟化酶阳性神经元的丢失和损伤纹状体中多巴胺浓度的下降。此外，ACS84 可逆转体内丙二醛水平的升高和谷胱甘肽水平的降低。综上所述，ACS84 可能通过抗氧化机制预防神经退行性变，对帕金森病具有潜在的治疗价值。

https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3c/3616069/a9e90cd3fdf5/pone.0060200.g007.jpg
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https://cdn.ncbi.nlm.nih.gov/pmc/blobs/be3c/3616069/2cc9edb02a70/pone.0060200.g002.jpg
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