不对称二甲精氨酸含量及氧化应激与阿尔茨海默病发病的关系研究

The correlation of asymmetrical dimethylarginine level and oxidative stress to the onset of Alzheimer's disease

为探讨不对称二甲基精氨酸(ADMA)含量及氧化应激与AD发病的关系,抽取34例正常人及37例AD患者脑脊液样本,比较分析了脑脊液内ADMA、Aβ40/Aβ42蛋白比例、一氧化氮(NO)、诱导型一氧化氮合成酶(iNOS)活性及丙二醛(MDA)、3-硝基酪氨酸(3-NT)、过氧亚硝基(ONOO-)的含量差异,分析了ADMA含量与诸因素间及其与AD症状的相关性,以阐明其与AD发病的关系。结果表明,AD患者脑脊液中ADMA含量显著低于正常对照组,其水平与NO、iNOS含量及Aβ40/Aβ42比例均呈显著负相关,与MMSE评分呈正相关。AD患者脑脊液中3-NT、MDA及Ras浓度均显著高于正常对照组(P<0.05)。本研究结果表明,联合调节体内ADMA代谢水平及氧化应激可能为AD的预防及临床治疗提供新思路。

This study is to investigate the influence and mechanism of action of asymmetrical dimethyl-arginine （ADMA） and the induced oxidative stress level on Alzheimer＇s disease （AD） incidence. ADMA concentration,nitric oxide,Aβ40/Aβ42 ratio,inducible NO synthase （iNOS） activity and the concentrations of the induced free radicals including malondialdehyde （MDA）,3-nitrotyrosine （3-NT） and peroxynitrite （ONOO-） in the cerebrospinal fluid （CSF） from 34 neurologically normal controls and 37 AD patients were quantitatively determined and statistically compared. The results showed that the ADMA concentration significantly decreased in AD patients,and it showed negative correlation with the NO,iNOS activity,and showed positive correlation with MMSE score. ADMA concentration was negatively correlated with Aβ40/Aβ42 ratio （P 0.01） with the observation that Aβ40/Aβ42 ratio increased while ADMA level decreased in CSF in AD patients. The concentration levels of MDA,3-NT and ROS significantly increased compared with the control with all the P values less than 0.05. These findings suggested that the ADMA disorder and the oxidative damage effect of the induced free radicals in CSF of AD patients are an important mechanism of AD incidence,and their joint regulation may provide new idea for the prevention and clinical treatment of AD.