1,5-二咖啡酰奎宁酸对MPP^+所致PC12细胞损伤的保护作用  

Protective Effects of 1,5-Dicaffeoylquinic Acid against MPP^+ Induced Neurotoxicity of PC12 Cells

作　　者：曹旭[1,2] 肖海兵[1] 李慧[1] 孙圣刚[1] 褚晓凡[3] 

机构地区：[1]华中科技大学同济医学院附属协和医院神经内科,武汉430022 [2]武汉市中心医院神经内科,武汉430014 [3]暨南大学第二临床学院神经内科,深圳518020

出　　处：《华中科技大学学报（医学版）》2010年第4期435-438,465,共5页Acta Medicinae Universitatis Scientiae et Technologiae Huazhong

基　　金：国家自然科学基金资助项目(No.30570627)

摘　　要：目的探讨1,5-二咖啡酰奎宁酸(1,5-dicaffeoylquinic acid,1,5-diCQA)对多巴胺能神经元的保护作用及其可能的机制。方法采用1-甲基-4-苯基吡啶离子(MPP+)诱导具有多巴胺能神经元特性的PC12细胞作为帕金森病的体外模型,实验分为正常对照组、MPP+组和1,5-diCQA预处理组,根据1,5-diCQA预处理的浓度,将后者又分为10、20、50、100μmol/L 4组。用MTT法测定各组细胞存活率,酶标仪检测细胞活性氧簇(reactive oxygen species,ROS)含量和谷胱甘肽(glutathione,GSH)水平,RT-PCR法检测细胞突触核蛋白(α-synuclein)的mRNA表达水平,Western blot检测各组细胞α-synuclein蛋白表达水平。结果 MPP+(250μmol/L)处理PC12细胞24 h后,与正常对照组相比,细胞存活率下降,ROS生成增多,GSH耗竭;不同浓度的1,5-diCQA预处理可以减轻MPP+导致的细胞损伤,且在一定范围内具有量-效关系;50μmol/L的1,5-diCQA预处理可以显著抑制MPP+诱导的α-synuclein转录和翻译水平的增加。结论 1,5-diCQA对MPP+诱导的PC12细胞氧化应激损伤具有浓度依赖性的抑制作用,并抑制α-synuclein的过表达,提示1,5-diCQA对帕金森病细胞模型具有保护作用。Objective To investigate the protective effects of 1,5 dicaffeoylquinic acid（1,5-diCQA）preconditioning on the injury of PC12 cells induced by MPP^＋ and the possible mechanisms. Methods MPP^＋ was added to make a model of Parkinson disease in rat pheochromocytoma（PC12） cells. PC12 cells were divided into three groups randomly ： control group, MPP^＋ group, 1,5-diCQA＋MPP^＋ group. Cell viability was determined by MTT assay. Cellular ROS and GSH were observed by a spectrophotometer. The expression of α-synuclein mRNA and protein was detected by using RT-PCR and Western blot respectively. Results ①The cell viability in MPP^＋ group was obviously less than in control group and 1,5-diCQA pretreatment＋ MPP^＋ group. ②The ROS production and cellular depletion was lessened by pretreatment of 1,5-diCQA in a dose-dependent manner. ③1,5-diCQA（50 μmol/L）pretreatment could inhibit the MPP^＋-induced up-regulation of the expression of α-synuclein mRNA and protein. Conclusion 1,5-diCQA may have a neuroprotective potential for it could attenuate the oxidative stress and α-synuclein overexpression in the PC12 cells induced by MPP^＋.

关 键 词：1 5-二咖啡酰奎宁酸 1-甲基-4-苯基吡啶离子 PC12细胞 帕金森病 

分 类 号：R742.5[医药卫生—神经病学与精神病学]