Chen Shih-Hsuan, Kuo Chung-Wen, Lin Tsu-Kung, Tsai Meng-Han, Liou Chia-Wei
Department of Neurology, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Core Laboratory for Phenomics and Diagnostics, Kaohsiung Chang Gung Memorial Hospital and Chang Gung University College of Medicine, Kaohsiung 83301, Taiwan.
Antioxidants (Basel). 2020 Nov 20;9(11):1159. doi: 10.3390/antiox9111159.
Few studies have reported on changes to oxidative stress and mitochondrial DNA copy numbers in patients with Parkinson's disease (PD), particularly those undergoing long-term dopamine therapy. This study measured mitochondrial copy numbers, thiobarbituric acid reactive substances (TBARS), and thiols in 725 PD patients and 744 controls. The total prescribed dopamine dose was calculated for each PD patient. A decreased mitochondrial copy number and antioxidant thiols level, but an elevated oxidative TBARS level presented in PD patients. Stratification into age subgroups revealed a consistently lower mitochondrial copy number and thiols in all PD subgroups, but increased TBARS levels compared with those of the controls. Further study found an association between lower serum TBARS and dopamine administration. There appears to be an indirect relationship with the mitochondrial copy number, where a decrease in TBARS was found to diminish the effect of pathogenetic and age-related decrease in mitochondrial copy number in PD patients. Follow-up evaluations noted more significant decreases of mitochondrial copy numbers in PD patients over time; meanwhile, dopamine administration was associated with an initial decrease of the TBARS level which attenuated with high-dose and long-term therapy. Our study provides evidence that moderate dopamine dose therapy benefits PD patients through attenuation of oxidative stress and manipulation of the mitochondrial copy number.
很少有研究报道帕金森病（PD）患者氧化应激和线粒体DNA拷贝数的变化，尤其是那些接受长期多巴胺治疗的患者。本研究测量了725例PD患者和744例对照者的线粒体拷贝数、硫代巴比妥酸反应性物质（TBARS）和硫醇。计算了每位PD患者的多巴胺总处方剂量。PD患者的线粒体拷贝数和抗氧化硫醇水平降低，但氧化TBARS水平升高。按年龄亚组分层显示，所有PD亚组的线粒体拷贝数和硫醇水平始终较低，但与对照组相比，TBARS水平升高。进一步研究发现血清TBARS降低与多巴胺给药之间存在关联。这似乎与线粒体拷贝数存在间接关系，即发现TBARS降低可减轻PD患者致病和年龄相关的线粒体拷贝数减少的影响。随访评估指出，随着时间的推移，PD患者的线粒体拷贝数下降更为显著；与此同时，多巴胺给药与TBARS水平的初始下降有关，而高剂量和长期治疗会使其减弱。我们的研究提供了证据，表明适度的多巴胺剂量治疗通过减轻氧化应激和控制线粒体拷贝数使PD患者受益。
