百草枯致神经细胞凋亡与帕金森病的相关性

摘要/Abstract

摘要： 帕金森病（Parkinson’s disease, PD）是一种以黑质纹状体中多巴胺能神经元选择性丢失为特征的神经变性疾病，其发病原因至今不详。多年来，遗传因素和环境因素一直是PD发病机制中研究争论的热点，然而，自发性的PD缺乏遗传因素的迹象，这就使环境因素在PD的病因学中占据了优势地位。百草枯（Paraquat, PQ）是一种结构与1-甲基-4-苯基-1，2，3，6-四氢吡啶（1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine, MPTP）的活性代谢物1-甲基-4-苯基-吡啶（1-methyl-4-phenylpyridinium, MPP⁺）相似的化学物质，而MPP+可诱导神经细胞发生毒性改变，促进神经细胞凋亡机制的发生。目前，有大量文献报道，农业中经常使用的除草剂PQ是PD发病的危险因素之一。本文提出以PQ诱导SH-SY5Y细胞为模型，进行PQ导致PD发病的机制研究。以确定PQ是通过类似于MPP⁺诱导细胞凋亡途径导致PD的发病，还是通过引起细胞内氧化应激的发生或者线粒体功能障碍、蛋白酶体异常等途径导致了PD的发病。并且，进一步研究PQ导致PD发生的分子机制，将对PD的预防和治疗有其重要意义。

关键词: 帕金森病, 百草枯, 凋亡

Abstract: Parkinson’s disease (PD) is a neurodegenerative disorder characterized by selective loss of dopaminergic neurons in the substantia nigra (SN); however, the causes of PD remain unknown. Over the years the etiologic involvement of genetic inheritance versus environmental exposures has been under debate. In this sense, a lack of evidence for heritability of the idiopathic PD has pointed to environmental risk factors as potential contributors to the disease etiology. It is reported that, Paraquat (PQ) (1,1-dimethyl-4,4′-bipyridinium dichloride), a widely used herbicide, was suggested as a potential etiologic factor for the development of PD. Paraquat is structurally similar to the neurotoxin MPP+ (1-methyl-4-phenylpyridinium), the latter being an active metabolite derived from MPTP (1- methyl-4-phenyl-1,2,3,6-tetrahydropyridine) and being capable of inducing the apoptosis of neural cells. In this paper, we used the model of PQ induced toxicity on SH-SY5Y to study the mechanism underlying its effect in causing dopaminergic cells degeneration and necrosis. To this end, we determined whether PQ activated apoptotic pathways leading to the pathogenesis of PD as MPP+ does, or caused intracellular oxidative stress， mitochondrial dysfunction or proteasome abnormality to induce PD. Intensive study of the molecular mechanisms for PQ induction of PD will be of great value for the prevention and treatment of PD.

Key words: Parkinson&, rsquo, s disease, Paraquat, apoptosis

中图分类号:

R742，R964

田小菲，李建锋，庞灏. 百草枯致神经细胞凋亡与帕金森病的相关性[J]. 神经药理学报, 2011, 1(5): 27-33.

TIAN Xiao-fei, LI Jian-feng, PANG Hao. Paraquat-induced Neuronal Apoptosis Associated with Parkinson's Disease[J]. Acta Neuropharmacologica, 2011, 1(5): 27-33.

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