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线粒体氧化损伤和氧化性DNA损伤的增加促成了散发性肌萎缩侧索硬化症的神经退行性病变过程。

Increased mitochondrial oxidative damage and oxidative DNA damage contributes to the neurodegenerative process in sporadic amyotrophic lateral sclerosis.

作者信息

Murata Takahiko, Ohtsuka Chigumi, Terayama Yasuo

机构信息

Department of Neurology, Iwate Prefectural Ninohe Hospital, Ninohe, Iwate, Japan.

出版信息

Free Radic Res. 2008 Mar;42(3):221-5. doi: 10.1080/10715760701877262.

DOI:10.1080/10715760701877262
PMID:18344116
Abstract

To investigate the possibility that mitochondrial oxidative damage or oxidative DNA damage or both contribute to the neurodegenerative process of sporadic amyotrophic lateral sclerosis (sALS), this study used high-performance liquid chromatography with an electrochemical detector to measure the concentrations of the reduced and oxidized forms of coenzyme Q10 (CoQ10) and 8-hydroxy-2'-deoxyguanosine (8-OHdG) in the cerebrospinal fluid (CSF) of 17 patients with sALS and 17 age-matched controls with no neurological diseases. The percentage of oxidized CoQ10 in the CSF of sALS patients was greater than that in the CSF of controls (p<0.002) and was negatively correlated with the duration of illness (rho=-0.61, p<0.01). The concentration of 8-OHdG in the CSF of sALS patients was greater than that in the CSF of controls (p<0.005) and was positively correlated with the duration of illness (rho=0.53, p<0.005). The percentage of oxidized CoQ10 was correlated with the concentrations of 8-OHdG in the CSF of sALS patients (rho=-0.53, p<0.05). These results suggest that both mitochondrial oxidative damage and oxidative DNA damage play important roles in the pathogenesis of sporadic amyotrophic lateral sclerosis.

摘要

为了研究线粒体氧化损伤或氧化性DNA损伤或两者共同作用是否导致散发性肌萎缩侧索硬化症(sALS)的神经退行性变过程,本研究采用高效液相色谱-电化学检测器来测量17例sALS患者和17例年龄匹配的无神经疾病对照者脑脊液(CSF)中辅酶Q10(CoQ10)还原型和氧化型以及8-羟基-2'-脱氧鸟苷(8-OHdG)的浓度。sALS患者脑脊液中氧化型CoQ10的百分比高于对照组脑脊液中的百分比(p<0.002),且与病程呈负相关(rho=-0.61,p<0.01)。sALS患者脑脊液中8-OHdG的浓度高于对照组脑脊液中的浓度(p<0.005),且与病程呈正相关(rho=0.53,p<0.005)。sALS患者脑脊液中氧化型CoQ10的百分比与8-OHdG的浓度相关(rho=-0.53,p<0.05)。这些结果表明,线粒体氧化损伤和氧化性DNA损伤在散发性肌萎缩侧索硬化症的发病机制中均起重要作用。

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