Abstract

目的 研究慢性脑缺血大鼠海马中DNA损伤修复相关蛋白脱嘌呤/脱嘧啶核酸内切酶/氧化还原因子-1(APE/Ref-1)的活性变化与神经元的凋亡,并探讨两者之间的相关性.方法成年雄性Wistar大鼠40只,随机分为假手术组,持久性双侧颈总动脉结扎(2-VO)1周组、3周组、8周组,每组各10只,用Western blotting检测其APE蛋白表达水平的变化,并用流式细胞仪定量检测海马神经元的凋亡程度.结果2-VO1周组APE蛋白的表达量明显下降,与对照组相比差异有显著性(P＜0.01),随后其蛋白表达水平逐渐上升,但仍低于对照组水平(P＜0.05);用流式细胞仪检测各组的凋亡率发现2-VO 1周组、3周组凋亡率较高,与对照组相比差异有显著性(P＜0.01).结论慢性脑缺血早期DNA修复蛋白APE活性下降,同时其神经元凋亡率较高,后期蛋白表达水平逐渐上升,神经元的凋亡程度也逐渐下降,表明DNA损伤与修复失衡所致的神经元凋亡是慢性缺血性脑损伤发病的重要机制。

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