Department of Medicine, National University of Singapore, Singapore.
Free Radic Biol Med. 2010 Feb 15;48(4):560-6. doi: 10.1016/j.freeradbiomed.2009.11.026. Epub 2009 Dec 4.
Oxidative damage has been implicated in the pathogenesis of Parkinson disease (PD) but the literature data are confusing. Using products of lipid and DNA oxidation measured by accurate methods, we assessed the extent of oxidative damage in PD patients. The levels of plasma F(2)-isoprostanes (F(2)-IsoPs), hydroxyeicosatetraenoic acid products (HETEs), cholesterol oxidation products, neuroprostanes (F(4)-NPs), phospholipase A(2) (PLA(2)) and platelet activating factor-acetylhydrolase (PAF-AH) activities, urinary 8-hydroxy-2'-deoxyguanosine (8-OHdG), and serum high-sensitivity C-reactive protein were compared in 61 PD patients and 61 age-matched controls. The levels of plasma F(2)-IsoPs, HETEs, 7beta-and 27-hydroxycholesterol, 7-ketocholesterol, F(4)-NPs, and urinary 8-OHdG were elevated, whereas the levels of plasma PLA(2) and PAF-AH activities were lower, in PD patients compared to controls (p< 0.05). The levels of plasma F(2)-IsoPs, HETEs, and urinary 8-OHdG were higher in the early stages of PD (p trend< 0.05). There was a significant negative correlation between the cumulative intake of levodopa and urinary 8-OHdG (r= -0.305, p= 0.023) and plasma total HETEs (r= -0.285, p= 0.043). Oxidative damage markers are systemically elevated in PD, which may give clues about the relation of oxidative damage to the onset and progression of PD.
氧化损伤与帕金森病(PD)的发病机制有关,但文献资料存在争议。本研究采用准确的方法测定脂质和 DNA 氧化产物,评估 PD 患者氧化损伤的程度。结果发现,与对照组相比,61 例 PD 患者的血浆 F2-异前列腺素(F2-IsoPs)、羟二十碳四烯酸产物(HETEs)、胆固醇氧化产物、神经前列腺素(F4-NPs)、磷脂酶 A2(PLA2)和血小板激活因子乙酰水解酶(PAF-AH)活性、尿 8-羟基-2'-脱氧鸟苷(8-OHdG)和血清高敏 C 反应蛋白水平均升高(p<0.05)。而且,PD 患者的血浆 PLA2 和 PAF-AH 活性水平降低(p<0.05)。与对照组相比,PD 患者的血浆 F2-IsoPs、HETEs 和尿 8-OHdG 水平在疾病的早期阶段升高(p 趋势<0.05)。左旋多巴累积摄入量与尿 8-OHdG(r=-0.305,p=0.023)和血浆总 HETEs(r=-0.285,p=0.043)呈显著负相关。氧化损伤标志物在 PD 患者中全身性升高,这可能提示氧化损伤与 PD 的发病和进展有关。