β-淀粉样多肽神经毒性的氧化应激机制和褪黑素神经保护机制研究  

The experimental studies on oxidative stress mechanisms of neurotoxic effects of β-amyloid peptide and the antioxidative mechanism of neuronal protective effects of Melatonin

作　　者：叶静[1] 刘协和[2] 邓红[2] 王英成[2] 李胜富[3] 

机构地区：[1]首都医科大学宣武医院神经内科,北京100053 [2]四川大学华西医院精神科 [3]四川大学华西医院移植免疫室

出　　处：《中华精神科杂志》2002年第4期212-215,共4页Chinese Journal of Psychiatry

基　　金：国家"973"计划项目 (G2 0 0 0 0 570 0 5);中国博士后基金资助项目 ( 99 10 )

摘　　要：目的　观察氧化应激在 β 淀粉样多肽 (Aβ)神经毒性的介导作用和褪黑素 (Mel)神经保护作用的抗氧化机制 ,为老年性痴呆的抗氧化治疗提供依据。方法　新生大鼠原代神经元培养 ,分为实验组 (A1 ,B1 ,C1 ,D1 组 )、治疗组 (A2 ,B2 ,C2 ,D2 组 )和空白对照组。实验组四组分别暴露浓度为 0 5 ,1 0 ,1 0 0 ,2 0 0 μmol/L的Aβ2 5 35,治疗组四组同时暴露 1 0 μmol/LMel。比色法测定丙二醛 (MDA)、还原型谷胱甘肽 (GSH)水平以及过氧化氢酶 (CAT)和谷胱甘肽过氧化物酶 (GSH Px)活力 ,并用MTT法测定培养神经元细胞存活率。统计学方法采用方差分析、t检验和相关分析。结果　细胞存活率与Aβ浓度呈显著性负相关 (r=- 0 834 ,P <0 0 0 1 )。MDA :实验组 (A1 ,B1 ,C1 ,D1 组 ,以下同 )分别为 (2 1±0 5)nmol/L ,(3 1± 0 5)nmol/L ,(4 8± 0 9)nmol/L ,(6 0± 0 6)nmol/L ;治疗组 (A2 ,B2 ,C2 ,D2 组 ,以下同 )分别为 (1 9± 0 3)nmol/L ,(2 3± 0 3)nmol/L ,(2 8± 0 5)nmol/L ,(2 9± 0 4)nmol/L ;对照组为(1 6± 0 2 )nmol/L。GSH :实验组分别为 (8 3± 1 5)g/L ,(5 8± 1 7)g/L ,(4 4± 1 3)g/L ,(3 7± 0 5)g/L ,治疗组分别为 (9 9± 1 6)g/L ,(7 7± 1 7)g/L ,(6 3± 1 2 )g/L ,Objective To study the mechanisms of oxidative stress induced by β amyloid peptide(Aβ) and the mechanisms of antioxidative role by Melatonin , and to provide the experimental evidence for antioxidative treatment in Alzheimer disease Methods Themalondialdehydeacid(MDA), glutathione(GSH),glutathione peroxidase(GSH Px),Catalase(CAT), were measured by chromatometry,and rate of cell viability was analysied by MTT method from the medium of cultured neurons The statistical analyses used were the independent samples T test and correlate analysis Results MTT analysis indicated that Aβ induced the death of cultured neuronal cell, and the rate of cell viability was negatively correlated with the Aβ concentration ( r =-0 834, P <0 001) Aβ dose dependently increased the level of MDA, decreased the level of GSH, decreased the activity of CAT and GSH Px. Melatonin had a role in antagonising the neurotoxicity of Aβ Conclusions Aβ can induce the death of cultured neurons, and the oxidative stress mechanism may be involved in the neurotoxicity of Aβ Melatonin can be pertly against the neurotoxicity of Aβ by reducing the level of lipid peroxidative andincreasing the activity of antioxidant enzyme

关 键 词：β-淀粉样多 肽神经毒性 氧化性应激 褪黑激素 老年性痴呆 抗氧化疗法 

分 类 号：R749.1[医药卫生—神经病学与精神病学]