摘要
为研究脑缺血 再灌流后氧化性DNA损伤及阿魏酸钠的保护作用 ,采用线栓法制成大鼠大脑中动脉阻塞及再通模型。大脑中动脉再通时静脉注射阿魏酸钠 (15mg/kg) ,用免疫组织化学方法检测脑缺血 2h ,再灌流 4 8h后缺血再灌流组、阿魏酸钠组及对照组脑组织再灌流后氧化性DNA损伤产物 8 羟基脱氧鸟苷(8 OHdG)的表达。结果发现对照组脑区仅见少数散在微弱的 8 OHdG阳性表达 ;缺血再灌流组大脑中动脉阻塞侧额顶叶上部皮质和内侧尾壳核脑区有大量的 8 OHdG阳性表达 ,较对照组显著增加 (P <0 .0 1) ;阿魏酸钠组 8 OHdG阳性表达在脑区分布与缺血再灌流组相似 ,但较缺血再灌流组显著减少 (P <0 .0 1)。上述结果表明脑缺血—再灌流所致的氧化性DNA损伤主要存在于缺血半暗带 ,阿魏酸钠对氧化性DNA损伤具有保护作用。
We created a model of cerebral ischemia-reperfusion in Wistar rats. Ischemia was induced by occluding middle cerebral artery with intraluminal filament for 2 h, then the circulation was restored for 48 h. Sham operations were performed in control rats. Sodium ferulate (15 mg/kg) or saline was intravenously administered at 2 h after middle cerebral artery occlusion. The extent of oxidative DNA damage in rat brain at the end of 48 h after reperfusion was by examined immunohistochemical analysis for 8-hydroxy-2'-deoxyguanosine (8-OHdG), a biomarker of oxidative DNA damage. There was very weak 8-OHdG immunoreactivity in sham-operated brain. In the ischemia-reperfusion rats, however, the intensity of 8-OHdG immunoreactivity was markedly increased (P<0.01) mainly located at medial caudoputamen and upper frontoparietal cortex, the area just at the boundary zone of middle cerebral artery. The level of 8-OHdG in the sodium ferulate administration group was significantly lower than saline administration group. The findings of the present study suggest oxidative DNA damage involved in neuron injury in ischemic penumbra and sodium ferulate may protect against the ischemia-reperfusion induced oxidative DNA damage in rat brain.
基金
湖北省自然科学基金! (99J12 6)
湖北省教委科研基金! (99B0 0 9)
