姜黄素对帕金森病多巴胺能神经元的保护作用及其机制
[Protective effect of curcumin on dopamine neurons in Parkinson's disease and its mechanism].
作者信息
Wu You, Liang Shunli, Xu Bin, Zhang Rongbo, Xu Linsheng
机构信息
Department of Neurology, the Second Affiliated Hospital of Zhejiang Chinese Medical University, Hangzhou 310005, China.
出版信息
Zhejiang Da Xue Xue Bao Yi Xue Ban. 2018 May 25;47(5):480-486. doi: 10.3785/j.issn.1008-9292.2018.10.06.
OBJECTIVE
To investigate the effect of curcumin on dopamine neurons in Parkinson's disease (PD) and its mechanism.
METHODS
SH-SY5Y human neuroblastoma cells were treated with 1-methyl-4-phenyl-1,2,3,6-tetrahydropyridine (MPTP) to establish the PD cell model. The model cells were treated with curcumin and/or autophagy inhibitor 3-MA. After 48 h of drug treatment, the number of surviving dopamine neurons was detected by tyrosine hydroxylase immunofluorescence method. Western blotting was used to detect protein expression of α-Synuclein (α-Syn), transcription factor EB (TFEB) and autophagy-related proteins lysosome-associated membrane protein 2A (LAMP2A) and microtubule-associated protein 1 light chain 3-Ⅱ(LC3-Ⅱ); RT-PCR was used to detect mRNA expression of α-Syn.
RESULTS
Compared with MPTP model group, curcumin increased the number of surviving dopamine neurons(<0.01), decreased both protein expression and mRNA expression of α-Syn (all <0.01), and increased protein expression of TFEB, LAMP2A and LC3-Ⅱ (all <0.01). When curcumin and 3-MA were given concurrently, the number of surviving dopamine neurons, protein expression of TFEB, LAMP2A and LC3-Ⅱ increased (<0.05 or <0.01), and both protein expression and mRNA expression of α-Syn decreased (<0.05 or <0.01) compared with MPTP model group; but the number of surviving dopamine neurons and protein expression of LAMP2A and LC3-Ⅱ decreased compared with curcumin group (all <0.05).
CONCLUSIONS
Curcumin exerts protective effect on dopamine neurons in PD, which may be associated with enhancing autophagy and promoting the clearance of α-Syn.
目的
探讨姜黄素对帕金森病（PD）中多巴胺能神经元的作用及其机制。
方法
用1-甲基-4-苯基-1,2,3,6-四氢吡啶（MPTP）处理人神经母细胞瘤SH-SY5Y细胞，建立PD细胞模型。将模型细胞用姜黄素和/或自噬抑制剂3-甲基腺嘌呤（3-MA）处理。药物处理48小时后，采用酪氨酸羟化酶免疫荧光法检测存活多巴胺能神经元的数量。用蛋白质印迹法检测α-突触核蛋白（α-Syn）、转录因子EB（TFEB）和自噬相关蛋白溶酶体相关膜蛋白2A（LAMP2A）及微管相关蛋白1轻链3-Ⅱ（LC3-Ⅱ）的蛋白表达；用逆转录-聚合酶链反应（RT-PCR）检测α-Syn的mRNA表达。
结果
与MPTP模型组相比，姜黄素增加了存活多巴胺能神经元的数量（<0.01），降低了α-Syn的蛋白表达和mRNA表达（均<0.01），并增加了TFEB、LAMP2A和LC3-Ⅱ的蛋白表达（均<0.01）。当姜黄素与3-MA同时给予时，与MPTP模型组相比，存活多巴胺能神经元的数量、TFEB、LAMP2A和LC3-Ⅱ的蛋白表达增加（<0.05或<0.01），α-Syn的蛋白表达和mRNA表达降低（<0.05或<0.01）；但与姜黄素组相比，存活多巴胺能神经元的数量以及LAMP2A和LC3-Ⅱ的蛋白表达降低（均<0.05）。
结论
姜黄素对PD中的多巴胺能神经元具有保护作用，这可能与增强自噬和促进α-Syn的清除有关。
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