百草枯致神经细胞凋亡与帕金森病的相关性  

Paraquat-induced Neuronal Apoptosis Associated with Parkinson’s Disease

作　　者：田小菲[1,2] 李建锋[2] 庞灏[1] 

机构地区：[1]中国医科大学法医学院法医血清教研室 [2]河北北方学院基础医学院法医系

出　　处：《神经药理学报》2011年第5期27-33,共7页Acta Neuropharmacologica

基　　金：国家自然科学基金(No.30771833)

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,使环境因素在PD的病因学中占据主导地位。百草枯(Paraquat,PQ)是一种与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+)结构相似的化学物质,而MPP+可诱导神经细胞发生毒性改变,促进神经细胞凋亡的发生。目前,有大量文献报道,农业生产中经常使用的除草剂PQ是PD发病的危险因素之一。本文通过探讨PQ诱导SH-SY5Y细胞模型与PQ导致PD发病机制的相关性,以期进一步阐明PQ的致病机制是通过类似于MPP+诱导细胞凋亡还是通过引起胞内氧化应激的发生或是线粒体功能障碍、蛋白酶体异常等实现的,对临床进一步预防和治疗PD具有重要意义。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）, 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. This paper was aimed to discuss the relationship between the pathogenic mechanism of the PQ leading to PD and the model of PQ-induced SH-SY5Y cells, then to elucidate whether the pathogenic mechanism of the PQ is similar with MPP＋ induced apoptosis, or through the intracellular oxidative stress, or mitochondrial dysfunction and abnormal proteasome. This research will significantly help to prevent and treat with PD in clinical.

关 键 词：帕金森病 百草枯 凋亡 

分 类 号：R742[医药卫生—神经病学与精神病学] R964[医药卫生—临床医学]