Liu Hao, Uno Masaaki, Kitazato Keiko T, Suzue Atsuhiko, Manabe Shiji, Yamasaki Hiroyuki, Shono Masayuki, Nagahiro Shinji
Department of Neurosurgery, School of Medicine, The University of Tokushima, 3-18-15 Kuramoto-cho, Tokushima 770-8503, Japan.
Brain Res. 2004 Oct 29;1025(1-2):43-50. doi: 10.1016/j.brainres.2004.07.071.
Oxidative stress contributes to post-ischemic brain damage. We assessed the correlation between plasma 8-hydroxy-2'-deoxyguanosine (8-OHdG), as a marker of oxidative DNA damage, and progressive brain damage in rats subjected to transient or permanent ischemia. Male Wistar rats were subjected to permanent- and 0.5-, 1-, 2-h middle cerebral artery occlusion (MCAO). At various times thereafter, the infarct volume, 8-OHdG levels in plasma and brain tissue, DNA fragmentation, and immunohistochemical observations on their brains were recorded and compared. At 12 h after 2-h MCAO-reperfusion, the cortical infarct volume was increased; it peaked at 24 h. DNA degeneration expanded from the caudate putamen into the cortical region at 12 h. 8-OHdG-containing cells in the cortical infarct zone were observed at 12 h, the number of 8-OHdG-positive cells was highest at 24 h and they co-localized with DNA single-strand breaks. Plasma 8-OHdG significantly increased at 12 h, and peaked at 24 h after reperfusion (1.1+/-0.7 ng/ml (mean+/-S.D.); controls 0.3+/-0.1; p<0.01). This increase was in step with increased infarct volume, DNA degradation, and reflected immunohistochemical findings in the cortical region but not the caudate putamen. In the permanent MCAO model, plasma 8-OHdG levels were associated with the brain contents of 8-OHdG. Plasma 8-OHdG and the cortical infarct volume were lower in the 0.5- and 1-h than the 2-h MCAO model. Our findings suggest that 8-OHdG as a peripheral biomarker may be an indicator of oxidative brain damage in acute cerebral infarction.
氧化应激导致缺血后脑损伤。我们评估了作为氧化DNA损伤标志物的血浆8-羟基-2'-脱氧鸟苷(8-OHdG)与短暂或永久性缺血大鼠进行性脑损伤之间的相关性。雄性Wistar大鼠接受永久性和0.5、1、2小时的大脑中动脉闭塞(MCAO)。此后在不同时间记录并比较梗死体积、血浆和脑组织中的8-OHdG水平、DNA片段化以及对其大脑的免疫组织化学观察结果。在2小时MCAO再灌注后12小时,皮质梗死体积增加;在24小时达到峰值。DNA变性在12小时时从尾状壳核扩展到皮质区域。在12小时时观察到皮质梗死区含8-OHdG的细胞,8-OHdG阳性细胞数量在24小时时最高,且它们与DNA单链断裂共定位。再灌注后12小时血浆8-OHdG显著增加,在24小时达到峰值(1.1±0.7 ng/ml(平均值±标准差);对照组为0.3±0.1;p<0.01)。这种增加与梗死体积增加、DNA降解同步,并反映了皮质区域而非尾状壳核的免疫组织化学结果。在永久性MCAO模型中,血浆8-OHdG水平与大脑中8-OHdG含量相关。0.5小时和1小时MCAO模型中的血浆8-OHdG和皮质梗死体积低于2小时MCAO模型。我们的研究结果表明,8-OHdG作为一种外周生物标志物可能是急性脑梗死中氧化脑损伤的一个指标。