Biochemistry and Molecular Biology Research Center, Hospital Universitari Vall d'Hebron, Barcelona, Spain.
Stroke. 2010 Apr;41(4):653-60. doi: 10.1161/STROKEAHA.109.571935. Epub 2010 Feb 25.
Animal models of transient ischemia suggest that oxygen-derived free radicals produced on reperfusion of ischemic brain could constitute the main cause of reperfusion injury. We aimed to determine the presence and role of lipid peroxidation and protein oxidation-related molecules after tissue plasminogen activator-induced recanalization in human stroke.
A total of 160 patients with strokes involving the middle cerebral artery and treated with tissue plasminogen activator and 60 healthy controls were included. Blood samples, transcranial Doppler recordings, and National Institutes of Health Stroke Scale scores were obtained at baseline (pretreatment), 1 hour and 2 hours after tissue plasminogen activator bolus, and 12 hours and 24 hours after stroke onset. The main lipid peroxidation end-product malondialdehyde, advanced oxidation protein products, and plasma concentrations of myeloperoxidase were assessed.
At baseline, all oxidative stress biomarkers were higher than in control subjects (P<0.01 for all comparisons). Malondialdehyde remained high compared with controls during the study period, whereas myeloperoxidase concentrations were significantly raised at baseline, 1 hour after tissue plasminogen activator administration, and 12 hours after stroke onset. Malondialdehyde concentrations correlated with stroke severity and were associated with outcome and with hemorrhagic complications. Regarding recanalization, among those patients with middle cerebral artery recanalization by the end of tissue plasminogen activator infusion (44%) or anytime thereafter, no peaking of any of the studied molecules could be identified.
Our study showed that systemic oxidative damage to lipids and proteins had already occurred at baseline in stroke. In contrast to animal studies, a relationship between free radical-mediated oxidative damage to lipids or proteins and reperfusion injury after arterial recanalization could not be established.
动物短暂性脑缺血模型表明，缺血性脑再灌注时产生的氧自由基可能是再灌注损伤的主要原因。我们旨在确定组织型纤溶酶原激活剂（tissue plasminogen activator，tPA）诱导再通后，人类脑卒中患者是否存在与脂质过氧化和蛋白氧化相关的分子及其作用。
共纳入 160 例大脑中动脉梗死且接受 tPA 治疗的患者和 60 例健康对照者。在基线（治疗前）、tPA 推注后 1 小时和 2 小时、脑卒中发病后 12 小时和 24 小时，采集血样、经颅多普勒超声记录和 NIH 卒中量表评分。评估主要脂质过氧化终产物丙二醛（malondialdehyde，MDA）、晚期氧化蛋白产物和髓过氧化物酶（myeloperoxidase，MPO）的血浆浓度。
基线时，所有氧化应激生物标志物均高于对照组（所有比较 P<0.01）。研究期间 MDA 水平一直高于对照组，而 MPO 浓度在基线时、tPA 给药后 1 小时和脑卒中发病后 12 小时显著升高。MDA 浓度与卒中严重程度相关，与结局和出血性并发症相关。关于再通，在 tPA 输注结束时（44%）或之后任何时间有大脑中动脉再通的患者中，没有发现任何研究分子的峰值。
我们的研究表明，脑卒中患者在基线时已经发生了系统性脂质和蛋白氧化损伤。与动物研究不同，未能证实动脉再通后脂质或蛋白自由基介导的氧化损伤与再灌注损伤之间存在关系。
